Lifesciences LLC Research Articles

Patterns and Predictors of Multiple Sclerosis Phenotype Transitions: A Longitudinal Analysis Using the CLIMB Study (P5-3.018)

Patterns and Predictors of Multiple Sclerosis Phenotype Transitions: A Longitudinal Analysis Using the CLIMB Study (P5-3.018)

Modulating CNS neuroinflammation in animal models of intracerebral hemorrhage by nasal anti-CD3 (S4.010)

<h3>Objective:</h3> Investigate the therapeutic benefit of nasal anti-CD3 treatment in animal model of ICH. <h3>Background:</h3> Intracerebral hemorrhage (ICH) is the most devastating type of stroke, with a disproportionately high mortality approaching 40%. Current investigations in ICH treatment have focused on limiting hematoma expansion which unfortunately, have not led to an effective treatment. Neuroinflammation play a critical role in secondary injury post-ICH. Exposure of brain parenchyma to blood products initiates a complex inflammatory cascade start with activation of resident microglia. Resulting cytokine release recruits circulating monocytes and lymphocytes, further enhancing inflammation, and contributing to secondary injury. The cellular and molecular mechanisms leading to neurological deficits following ICH are poorly understood, and there is no effective therapy to modulate the mitigate CNS injury and promote recovery. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells (Tregs). We found that nasal anti-CD3 monoclonal antibody induces IL-10-secreting Tregs that migrate to the brain and suppresses microglial inflammation in a mouse model of multiple sclerosis. The therapeutic potential of the Tregs/IL-10 axis in ICH is largely unexplored. <h3>Design/Methods:</h3> We employed the collagenases model of ICH in mice and administered nasal anti-CD3 treatment within 24 hours of ICH which was continued up to 1-month post-bleed. We performed Flow cytometry, histopathology and behavioral analyses to characterize the cells and assess the effects of treatment on the behavioral outcomes at 1-month post-ICH. <h3>Results:</h3> Nasal anti-CD3 increased FoxP3+ Tregs and IL10 producing FoxP3+ Tregs in the brain. It also reduced microglial activation and lesion volume in the ipsilateral hemisphere post-ICH. Treatment improved behavioral outcomes, including motor, spatial learning, and hippocampal-dependent working memory functions at 1-month post-ICH. <h3>Conclusions:</h3> Our findings suggest that the nasal anti-CD3 may represent a novel therapeutic approach for treating ICH and potentially other types of acute brain injury. <b>Disclosure:</b> Dr. Izzy has received publishing royalties from a publication relating to health care. Taha Yahya has nothing to disclose. Dr. Cao has nothing to disclose. Dr. Waed has nothing to disclose. Dr. Moreira has nothing to disclose. Dr. Rezende has nothing to disclose. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has received stock or an ownership interest from vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..

Cognitive Processing Speed Predicts Disability Milestones in Multiple Sclerosis (P5-3.014)

Cognitive Processing Speed Predicts Disability Milestones in Multiple Sclerosis (P5-3.014)

146-OR: Specific Metabolomic Signatures Associate with Diabetes Remission after Weight Loss

The response to weight loss intervention is heterogeneous both in weight loss amount and improvement in metabolism. We seek to identify biomarkers predictive of long-term weight loss and type 2 diabetes (T2D) remission in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies. Methods: LABS is a longitudinal observational study of 2458 consecutive cases (2006-2009) of bariatric surgery. Look AHEAD is an RCT comparing an intensive lifestyle intervention to T2D support and education in 5,145 U.S. adults with obesity and T2D enrolled between 2001-2004. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples from individuals selected based on sustained T2D remission (N=93 LABS, N=80 Look AHEAD) and extremes (top and bottom 13th percentile) of weight loss (N=151 LABS, 23 with T2D) at 4 or 5 years. We used PCA for dimensionality reduction of metabolites and logistic regression models to determine association between metabolic factors and phenotype. Improvement in model fit and net reclassification index analyses were performed to determine if metabolites improved a clinical model for predicting remission. Results: One factor composed of branched chain amino acids (BCAA) and tyrosine (p=0.045), and one composed of betaine and choline (p=0.02) were associated with T2D remission. Inclusion of these factors in a clinical prediction model improved the fit (p=0.04). Only one factor, composed of C31:1-C37:1 sphingomyelins, associated with weight loss at 5 years (p=0.036). Conclusions. Our findings define novel associations between metabolites in the BCAA and trimethylamine-N-oxide-microbiome-related pathways that are independently and incrementally associated with sustained T2D remission after weight loss. Future studies of these analytes could help in the discovery of metabolic regulatory mechanisms, and guide more personalized weight loss interventions in individuals with T2D. Disclosure L.C. Kwee: None. O. Ilkayeva: None. M. Muehlbauer: None. B.M. Wolfe: None. J.Q. Purnell: Advisory Panel; Self; Novo Nordisk A/S. H. Chen: None. C.B. Newgard: None. S.H. Shah: Research Support; Self; AstraZeneca, Verily Life Sciences LLC. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK108580)

77-LB: Improved A1C and TIR in Adults with T2D Participating in a CGM-Driven Virtual Diabetes Clinic

The Onduo Virtual Diabetes Clinic (VDC) for people with T2D combines a mobile app, remote personalized lifestyle coaching, connected devices and live video consultations with board-certified endocrinologists for medication management and prescription of real-time CGM devices for intermittent use. This prospective single-arm study enrolled adults with a baseline A1c of ≥8.0% to ≤12.0% from 2 primary care centers to participate in the VDC program. The primary outcome was change in A1c from baseline at 4 mo. Secondary outcomes included change in CGM-based (Dexcom G6) glycemic parameters. Participants (n=55) were: 57.3±11.6 yr, 40.0% female and BMI 33.7±7.2. A1c decreased significantly by -1.6%±1.0 (p&amp;lt;0.001) from 8.9%±1.0 to 7.3%±0.9 at 4 mo. Stratified by baseline A1c 8.0% to 9.0% (n=36) and &amp;gt;9.0% (n=19), A1c decreased by -1.2%±0.6 and -2.4%±1.3 (both p&amp;lt;0.001). CGM metrics (n=43) are presented in the Table. Percent time in range (TIR) increased significantly from below target to target levels at follow-up. The results indicate that participation in the VDC for 4 mo was associated with significant improvement in A1c, increased TIR, decreased time in hyperglycemia and no increase in hypoglycemia. In conclusion, the VDC has potential to support people with T2D and their clinicians between office visits by increasing access to specialty care and advanced diabetes technology including CGM. Disclosure A.R. Majithia: Consultant; Self; Onduo. C. Kusiak: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. A. Armento Lee: None. F.R. Colangelo: None. R. Romanelli: Advisory Panel; Self; Novo Nordisk Inc. S. Robertson: Other Relationship; Self; Verily Life Sciences LLC. D.P. Miller: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. D.M. Erani: None. R.F. Dixon: Employee; Self; Onduo. H. Zisser: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC.

12-OR: Participation in a Virtual Diabetes Clinic and Reduced Diabetes-Related Distress in Individuals with Type 2 Diabetes

Diabetes-related distress affects a significant proportion of adults with type 2 diabetes (T2D) and is associated with poor glycemic control and more problematic self-management. The Onduo Virtual Diabetes Clinic (VDC) is a telehealth program for people with T2D that combines mobile App technology, remote personalized lifestyle coaching, connected BG meters, real-time continuous glucose monitoring (rtCGM) devices and clinical support from board-certified endocrinologists. This exploratory analysis evaluated change in diabetes distress among 228 program participants who reported moderate distress (score 2.0-2.9) or severe distress (score ≥3.0) on the diabetes distress scale (DDS17) at enrollment. Change in diabetes-related distress was also compared for rtCGM vs. non-rtCGM user groups. Participants were age 51.8±9.5 years, 73.2% female and 39.5% were on insulin. During program participation, 94.7% used a connected BG meter and 33.8%, deemed to be high risk, used rtCGM intermittently. Participants reported significant reductions in overall DDS17 score, from 3.0±0.8 at baseline to 2.5± 0.9 (p&amp;lt;0.001) at an average of 6 months follow-up. Significant reductions in all DDS subscale scores were observed; most notable were reductions in the regimen-related and emotional distress subscales (-0.9 and -0.4, respectively; both p&amp;lt;0.001). Diabetes-related distress improved significantly in both CGM and non-rtCGM users. However, greater reductions in overall DDS17 score, -0.7 ± 0.8 vs. -0.4±0.9 (p=0.012), and regimen-related distress, -1.3±1.2 vs. -0.7±1.3 (p&amp;lt;0.001), were reported by participants who were prescribed and used intermittent rtCGM (n=77) vs. non-users (n=151). These findings suggest that the VDC program, which includes ongoing individualized lifestyle, clinical support and use of connected devices, may be an effective approach to support individuals with T2D and clinically relevant diabetes distress. Disclosure W.H. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Roche Diabetes Care. Consultant; Self; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk Inc., Onduo, Sanofi US, Xeris Pharmaceuticals, Inc. J.E. Layne: Employee; Self; Onduo. C.G. Parkin: Consultant; Self; Abbott, CeQur Corporation, Dexcom, Inc., DreaMed Diabetes, Novo Nordisk Inc., Onduo, Roche Diabetes Care, Valeritas, Inc. C. Kusiak: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. N.A. Barleen: Employee; Self; Onduo. D.P. Miller: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. H. Zisser: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. R.F. Dixon: Employee; Self; Onduo.

70-OR: Change in A1C with and without Intermittent Use of CGM in Adults with Type 2 Diabetes Participating in the Onduo Virtual Diabetes Clinic

The Onduo Virtual Diabetes Clinic (VDC) for people with T2D combines a mobile app, remote personalized lifestyle coaching and connected devices. Differentiating features are live video consultations with board-certified endocrinologists for medication management and prescription of real-time CGM devices for intermittent use as clinically indicated. This analysis examined change in A1c from enrollment to follow-up at 6 mo in CGM vs. non-CGM user groups. Characteristics of CGM (n=213) and non-CGM (n=399) groups were similar. Overall, participants (n=612) were 53.5±8.7 yr, 61.1% female and 26.5% lived in a rural geography. Baseline A1c was 7.8%±1.7, 33.0% were on insulin and 23.5% on a sulfonylurea. A1c decreased significantly in CGM and non-CGM groups by 0.9%±1.7 and 0.4%±1.3, respectively (both p&amp;lt;0.001). Change in A1c stratified by CGM use and baseline A1c categories of &amp;gt;9.0%, 8.0-9.0%, 7.0-&amp;lt;8.0%, &amp;lt;7.0% are presented in the Table. These real-world data suggest that participation in the Onduo VDC was associated with significant improvement in A1c for participants not meeting ADA treatment targets. There was an approximately two-fold greater improvement in A1c with intermittent CGM use. In conclusion, the VDC has potential to support people with T2D and their clinicians between office visits by increasing access to specialist care and advanced diabetes technology. Disclosure J.E. Layne: Employee; Self; Onduo. H. Zisser: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. R.M. Bergenstal: Consultant; Self; Ascensia Diabetes Care, Johnson &amp; Johnson. Other Relationship; Self; Abbott, Dexcom, Inc., Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Onduo, Roche Diabetes Care, Sanofi, UnitedHealth Group. R.A. Gabbay: Advisory Panel; Self; FormHealth, Health Reveal, Lark, Onduo, Vida Health. N.A. Barleen: Employee; Self; Onduo. D.P. Miller: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. R.F. Dixon: Employee; Self; Onduo.

526-P: Urine Tricarboxylic Acid Cycle Organic Anions and Progression of Diabetic Kidney Disease

Background: Urine tricarboxylic acid (TCA) cycle organic anions (OAs) are elevated in diabetes and may be biomarkers for diabetic kidney disease (DKD) progression. Methods: We conducted an ancillary study to the Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease (STOP-DKD) Trial - a randomized trial of pharmacist-led medication and behavior management in 281 patients with early to moderate DKD at Duke from 2014-2015. In this study, we used linear mixed models to assess associations of 10 urine TCA cycle OAs with estimated glomerular filtration rate (eGFR) and eGFR decline. TCA cycle OAs were measured in 24h urine samples by targeted MS and modeled as: (1) the average of z-scores for each OAs; and (2) factor scores derived by principal component analysis (PCA). We extended follow-up for eGFR to mid-2019 using electronic health records. Results: Among 132 participants (50% men; 58% Black; mean age 64 years [SD 9]; median eGFR 72 ml/min/1.73m2 [IQR 59-89] and urine albumin-to-creatinine [UACR] 25 mg/g [IQR 9-81]), PCA identified 3 OA metabolite factors (F). Fumarate, malate, α-ketoglutarate, citrate, lactate, and pyruvate loaded positively on F1; succinate, pyruvate, and lactate loaded negatively on F2; and methylsuccinate, ethylmalonate, and methylmalonate loaded positively on F3. Over a median follow-up of 1 year [IQR 1.3], higher average OA z score, F1, and F3 were each strongly associated with higher baseline eGFR after adjustment for age, sex, race, and log(UACR) at baseline (all p&amp;lt;0.01). Higher F2, but not other scores, was associated with faster eGFR decline (p=0.05). Conclusion: Lower urine TCA cycle OAs, most notably a factor comprising lower succinate, pyruvate and lactate, are potential biomarkers for faster DKD progression. Disclosure J. Lunyera: None. M. Nguyen: None. C.J. Diamantidis: None. H.B. Bosworth: Board Member; Self; Preventric Diagnostic. Consultant; Self; Abbott, Medicines Company, Novartis Pharmaceuticals Corporation. Research Support; Self; improved patient outcomes, Novo Nordisk Foundation, Otsuka Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pharma foundation, Proteus Digital Health, Proteus Digital Health, Sanofi. U.D. Patel: Board Member; Self; Goldfinch Bio. Employee; Self; Gilead Sciences, Inc. C.A. Davenport: None. J.R. Bain: None. M. Muehlbauer: None. O. Ilkayeva: None. S.H. Shah: Research Support; Self; AstraZeneca, Verily Life Sciences LLC. J. Scialla: Advisory Panel; Self; Tricida. Other Relationship; Self; GlaxoSmithKline plc., Sanofi. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK076169)

105-LB: Does HbA1c Accurately Predict Time-in-Range?

Background: Onduo’s Virtual Diabetes Clinic (VDC) incorporates a continuous glucose monitor (CGM), telemedicine, and a coaching app into the management of patients with type 2 diabetes (T2D). A recent meta-analysis of studies involving CGMs (Vigersky &amp; McMahon 2019) showed HbA1c and time in range (%TIR) are strongly correlated. Methods: All patients in the program with CGM usage in the 45 days prior to a follow-up HbA1c were analyzed. Mean HbA1c and %TIR were added to the previously published meta-analysis plot where each study or cohort is represented by a single dot. Additionally, a regression model was fit on the patient-level data. Results: Patient-level results from the VDC confirm the two metrics are strongly correlated (r=.-78). At the population-level, a mean %TIR of 84% in 194 VDC patients with mean HbA1c of 7.0% is 18% higher than predicted from the meta-analysis regression line. Cohorts associated with the 3 T2D studies in the meta-analysis were the 3 with the highest %TIR versus predicted, and 1 study with mixed type 1/2 was also higher than predicted. Conclusions: Our findings add support to the strong correlation observed between TIR and A1c overall, and suggest potentially distinct calibrations in T1D vs. T2D populations. Additional CGM data in T2D will clarify if separate prediction formulae are necessary. Disclosure R.F. Dixon: Employee; Self; Onduo LLC. D.P. Miller: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. A. Majithia: Consultant; Self; Onduo LLC. A. Armento Lee: Employee; Self; Verily Life Sciences LLC. S. Robertson: Employee; Self; Verily Life Sciences LLC. M. Germanos: None. H. Zisser: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC.

Digital Randomized Controlled Trial of Physical Activity Interventions (A Substudy of the MyHeart Counts Cardiovascular Health Study)

Background: Smartphone applications may enable interventions to increase physical activity but this has limited evidence in randomized trials. Objectives: The MyHeart Counts Cardiovascular Health study (MHC) is a smartphone-based longitudinal research study aimed at elucidating the determinants of cardiovascular health. Among MHC participants, we performed a randomized controlled trial to investigate the response to four different physical activity coaching interventions on the primary outcome of change in daily step count. Secondary outcomes included life satisfaction, 6-minute walk distance, and sleep quality. Methods: The trial was completed entirely using personal smartphones: participants were digitally consented, the interventions were delivered via the device, and measurements of the primary and secondary outcomes were collected from smartphone sensors. Participants were enrolled from December 12, 2016 to June 6, 2018 and followed for up to 5 weeks. Participants completed the trial through the MyHeart Counts phone app in a free-living setting. All adults over 18 years of age with access to a smartphone (Apple iPhone, version 5S or later) were eligible to participate. After one week of baseline measurements, participants (n=2783) were randomized to a sequence of four, week-long interventions delivered in random order. Interventions consisted of either daily prompts to complete 10,000 steps (completed by n=853); hourly prompts to stand following a full hour of sitting (completed by n=879); instructions to read the guidelines from the American Heart Association website (completed by n=868); and e-coaching based upon the individual's personal activity patterns from the baseline week of data collection (completed by n=896). Results: 2783 participants consented to enroll in the coaching study, of whom 1075 completed the baseline week of data collection and at least one of the four interventions. 493 individuals completed the full set of assigned interventions. All four interventions were found effective at modestly increasing daily step count by a mean of 266 ±75 steps from a baseline mean of 2958±69 steps (p=0.003). Intervention-specific step increases were: 319±74 steps (p<0.001) for the prompt to read the AHA Website, 267±74 steps (p<0.001) for the hourly stand prompt, 254±73 steps (p<0.001) for the participant-specific prompts, and 226±75 steps (p=<0.01 versus baseline) for the prompt to complete the daily 10,000 step goal. No significant effect of the interventions on any pre-specified secondary outcome was observed. Conclusions: The results indicate that four smartphone-based physical activity coaching interventions significantly increased daily physical activity in a short-term, randomized, controlled trial completed entirely using personal smartphones. Trial Registration: ClinicalTrials.gov Identifier NCT03090321 Funding Statement: The Division of Cardiovascular Medicine, Department of Medicine, Stanford University, received in-kind (software development) support from Apple Inc for the launch version of MHC. Software development since launch was funded by the Stanford Data Science Initiative. Steven Hershman is supported by The Division of Cardiovascular Medicine, Department of Medicine. Dr Sharma reports research grant support from the AHA Strategically Focused Research Network - Heart Failure (16SFRN30180010), Alberta Innovates Health Solution Clinician Scientist fellowship. Declaration of Interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. McConnell is an employee of Verily Life Sciences LLC. Dr Harrington is on the board of directors for Scanadu Inc (which is privately held) but reported receiving no consulting fees and reported having stock options with no current value. Dr Sharma reports research support from Roche Diagnostics, Takeda, BMS-Pfizer, and the Canadian Cardiovascular Society Bayer Vascular award. The remaining authors have nothing to disclose. Ethics Approval Statement: Ethical review and approval of the study was obtained from Stanford University’s Research Compliance Office (Protocol #IRB-31409).

A Promising Small Molecule for Vanishing White Matter Disease.

Investigators from Calico Life Sciences LLC and AbbVie report the effects of a novel drug targeting the genetic basis of Vanishing White Matter Disease (VWMD).

Human Regular U-500 Insulin via Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections in Adults with T2D—The VIVID Study—All Randomized Population

VIVID is the first prospective randomized controlled trial evaluating CSII (using an investigational Omnipod U-500™ Insulin Management System) vs. MDI (TID) with U-500R (Humulin® R U-500). This was a 26-week, open-label, multicenter, parallel study in adults with T2D on high dose insulin (201-600 units/day) with or without other antihyperglycemic agents (NCT02561078). We present results for the all randomized population (N=420); results for the primary population (excluding participants on concomitant GLP-1 RAs or SGLT2 inhibitors) are reported separately. Baseline characteristics were similar between arms. Without adjusting for multiplicity, CSII demonstrated significantly greater reduction in A1C and FPG at a lower total daily dose vs. MDI at 26 weeks. Also, a higher percentage of participants on CSII reached A1C targets &amp;lt;7.0%, &amp;lt;7.5%, and &amp;lt;8.0%. Severe hypoglycemia rates were low. Other hypoglycemia rates were similar (documented symptomatic) or higher (nocturnal) for CSII vs. MDI. Weight gain was similar (Table). In the all randomized population, U-500R via CSII demonstrated greater efficacy at a lower dose with a higher nocturnal hypoglycemia rate vs. MDI. CSII with U-500R may be a viable option for patients with T2D on high dose insulin. Individualized dose titration will be important for safely achieving glycemic targets. Disclosure G. Grunberger: Research Support; Self; Medtronic MiniMed, Inc., Novo Nordisk Inc.. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Janssen Pharmaceuticals, Inc.. A. Bhargava: None. T.T. Ly: Employee; Self; Insulet Corporation. H. Zisser: Employee; Self; Verily Life Sciences LLC.. Stock/Shareholder; Self; Verily Life Sciences LLC. L. Ilag: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J.K. Malone: Employee; Self; Eli Lilly and Company. S. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. J. Johnson: Employee; Self; Eli Lilly and Company.

Innovative Tailored Microlearning Approach to Insulin Self-Management Education Shows High Engagement Levels among Diverse Adults

Self-management education for adults with type 2 diabetes (T2DM) improves knowledge, skills and motivation; yet, new strategies to more effectively educate patients and improve adoption of insulin therapy are still needed. We conducted a prospective, non-randomized multi-center pilot, using a novel Patient Experience Cloud to deliver microlearning education focused on survival skills, insulin injection technique, and lifestyle management. Content was culturally relevant and tailored to minority patients with T2DM who recently initiated insulin treatment to enhance engagement. Consented T2DM adults, ages 20 to 70 years, were presented an online library of 56 education videos (1-4 minutes each). Pre and post surveys of self-reported attitudes towards insulin and patient activation measures (using the validated PAM scale) were obtained. The study enrolled 201 patients: 78 non-Hispanic whites (NHWs), 74 African Americans (AAs), 39 Hispanic whites (HWs) and 10 Other. Of these, 181 (90%) were engaged (defined as completing baseline surveys and watching 4+ videos). The number of videos viewed differed by race, p=0.012; with median number of 23 for AAs, 13 for NHWs and 5 for HWs. One week later, 83 participants (41%) continued engagement via viewing and completion of post questionnaires. Highest engagement was seen among AAs (51%) vs. 40% of NHWs and 26% of HWs. Overall attitudes towards insulin improved significantly, with a mean change of 0.29 points (on a 6 point Likert scale, 95% CI 0.02 to 0.56, p=0.03). Similarly, the PAM score increased significantly after viewing (by 0.17 point on a 4 point scale, 95% CI 0.to 0.26, p&amp;lt;0.001), independent of race. After viewing culturally tailored microlearning delivered via a cloud platform, patient attitudes towards insulin and activation measures for self-care improved significantly. This novel approach should be further investigated for its ability to improve adherence to insulin and glycemic outcomes. Disclosure M.M. Bogun: Other Relationship; Self; Mytonomy. N.E. Jelesoff: None. C.M. Nassar: None. C.R. Thacker: Other Relationship; Self; Amylin Pharmaceuticals, AstraZeneca, Mytonomy. J. Camacho Rivera: Research Support; Self; Mytonomy. C.J. Bourges: None. K. Sethi: None. L. Egbuonu-Davis: Employee; Self; Sanofi. A.C. Beal: Employee; Self; Sanofi. Board Member; Self; AcademyHealth. D.A. Greenwood: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Verily Life Sciences LLC.. Speaker's Bureau; Self; Becton, Dickinson and Company. Employee; Self; Mytonomy, Inc. Advisory Panel; Self; American Association of Diabetes Educators. H. Chatha: Employee; Self; Mytonomy. Employee; Spouse/Partner; Medstar Health. A. Kataria: Stock/Shareholder; Self; Mytonomy, Inc. Stock/Shareholder; Spouse/Partner; Mytonomy, Inc. D.B. McNeill: None. R. Goland: None. M.F. Magee: Research Support; Self; Sanofi, Eli Lilly and Company, MedStar Health Research Institute. Advisory Panel; Self; Merck &amp; Co., Inc.. Research Support; Self; PRIMED. Speaker's Bureau; Self; IMNE, American Diabetes Association. Advisory Panel; Self; Endocrine Society. Speaker's Bureau; Self; Sanofi. Research Support; Self; MedStar Health.

On-Demand, App-Delivered Coaching to Enable Diabetes Self-Management in Adults with Type 2 Diabetes—A Feasibility Study

Introduction: Diabetes self-management training (DSMT) is clinically effective but places a heavy burden on patients. Personalized coaching delivered via scalable mobile app platforms has the potential to provide much needed patient support. Objectives: This study assessed feasibility and participant experience of a new mobile app-based platform for delivering DSMT to people with type 2 diabetes (T2D). The primary objective was to evaluate participant enrollment (recruitment into the study and completing first sign-in). Engagement with app features and health coach for the study duration was also evaluated. Methods: Adults with T2D were enrolled into a 4-week prospective, single arm, observational study of the T2D App-based program. The T2D App provided medication reminders, meal logging, blood glucose (BG) tracking, and secure text messaging with a health coach. Participant engagement, satisfaction, participation in self-management behaviors, and finger stick BG results were also measured. Results: Of 67 participants recruited 99% (66) were able to sign-in to the app and 64 of 67 (96%) completed the 4-week program. The majority of program participants used the T2D App daily (median 100% of days, mean 95% of days). Engagement rates in coach messaging and BG logging exceeded 95% of subjects and were sustained across the study duration. Average blood glucose (AG) in the study participants decreased from week 1 to week 4 (mean -7.8 mg/dL, sd 20.3, P=0.008). The subgroup of individuals with starting AG greater than 154 mg/dL (n=13) experienced the largest declines in AG (mean -29.6 mg/dL, sd 17.9, P&amp;lt;0.0001). Conclusion: This initial feasibility study of a T2D App-based diabetes management program successfully enrolled participants and sustained their engagement. A decrease in AG was observed which, if sustained, would be clinically significant. Future studies with long term glycemic endpoints and an active control group are needed to validate this observation. Disclosure J.B. Hernandez: Employee; Self; Verily Life Sciences LLC.. A. Armento Lee: None. S. Robertson: Employee; Self; Verily Life Sciences LLC. C. Silver: Employee; Self; Verily Life Sciences LLC. A. Majithia: Employee; Self; Onduo.

Human Regular U-500 Insulin via Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections in Adults with T2D—The VIVID Study, Primary Population

VIVID is the first prospective, randomized controlled trial to assess efficacy and safety of U-500R (Humulin® R U-500) administered by CSII (using an investigational Omnipod U-500™ Insulin Management System) vs. MDI (TID). This 26-week, open-label, multicenter, parallel study (NCT02561078) enrolled adults with T2D on 201-600 units of insulin/day with or without other antihyperglycemic agents. We report data for the primary population (N=340), excluding participants on concomitant GLP-1 RAs or SGLT2 inhibitors. Data for the all-randomized population are reported separately. Baseline characteristics were similar between arms. CSII showed noninferior A1C reduction vs. MDI (primary objective) and superior FPG reduction at 26 weeks with adjustment for multiplicity. CSII showed significantly greater A1C reduction at a lower total daily dose with no multiplicity adjustment. Clinically important hypoglycemia rates (&amp;lt;54 mg/dL) and weight gain were similar; severe and nocturnal (≤70 mg/dL) hypoglycemia rates were statistically higher for CSII vs. MDI (Table). In this population, U-500R via CSII had greater efficacy at a lower dose vs. MDI with higher hypoglycemia rates for some categories. CSII with U-500R may be a viable option for T2D patients on high-dose insulin. Individualized dose titration will be important to safely achieve A1C targets. Disclosure G. Grunberger: Research Support; Self; Medtronic MiniMed, Inc., Novo Nordisk Inc.. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Janssen Pharmaceuticals, Inc.. A. Bhargava: None. T.T. Ly: Employee; Self; Insulet Corporation. H. Zisser: Employee; Self; Verily Life Sciences LLC.. Stock/Shareholder; Self; Verily Life Sciences LLC. L. Ilag: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J.K. Malone: Employee; Self; Eli Lilly and Company. S. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. J. Johnson: Employee; Self; Eli Lilly and Company.

Meeting of the minds

Allied Minds has partnered with Bristol-Myers Squibb to form Allied-Bristol Life Sciences LLC and can now add therapeutics to its portfolio of academia-based startups.

Flushing Profile of Extended-Release Niacin/Laropiprant Versus Gradually Titrated Niacin Extended-Release in Patients With Dyslipidemia With and Without Ischemic Cardiovascular Disease

Niacin has beneficial effects on a patient's lipid and lipoprotein profiles and cardiovascular risk, particularly at doses >2 g/day, but is underused due to flushing. Laropiprant (LRPT), a selective prostaglandin D(2) receptor-1 antagonist, decreases flushing associated with extended-release niacin (ERN). We compared flushing with ERN/LRPT dosed by a simplified 1-g --> 2-g regimen versus gradually titrated niacin extended-release (N-ER; given as NIASPAN, trademark of Kos Life Sciences LLC). Patients with dyslipidemia (n = 1,455) were randomized 1:1 to ERN/LRPT (1 g for 4 weeks advanced to 2 g for 12 weeks) or N-ER (0.5 g for 4 weeks titrated in 0.5-g increments every 4 weeks to 2 g for the final 4 weeks). Aspirin/nonsteroidal anti-inflammatory drugs were allowed to mitigate flushing. Flushing severity was assessed using the validated Global Flushing Severity Score (GFSS; none 0, mild 1 to 3, moderate 4 to 6, severe 7 to 9, extreme 10). Patients on ERN/LRPT, despite more rapid niacin titration, had less flushing than those on N-ER, as measured by number of days per week with moderate or greater GFSS across the treatment period (p <0.001). More than 2 times as many patients had no episodes of moderate, severe, or extreme flushing (GFSS > or =4) with ERN/LRPT than with N-ER (47.0% vs 22.0%, respectively) across the treatment period. Fewer patients on ERN/LRPT discontinued due to flushing than those on N-ER (7.4% vs 12.4%, p = 0.002). Other than the decrease in flushing, the safety and tolerability profile of ERN/LRPT was similar to that of N-ER. In conclusion, improvement in flushing with ERN/LRPT versus gradually titrated N-ER supports a rapidly advanced 1-g --> 2-g dosing regimen, allowing patients to start at 1 g and quickly reach and tolerate the optimal 2 g dose of ERN.

A comparison of the pharmacokinetics of two different formulations of extended-release niacin

ABSTRACTObjective: The objective of this study was to compare pharmacokinetic parameters of niacin extended-release tablets (NER uncoated) and niacin extended-release caplet formation (NER coated).* Niaspan is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USA† Niaspan CF is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USAResearch design and methods: Twenty-five healthy male and female subjects were enrolled in a four-period, open-label, randomized, crossover study. Both NER uncoated and NER coated were given as 1 × 1000 mg or 2 × 500 mg tablets. Similarity of NER coated 1 × 1000 mg and NER uncoated 2 × 500 mg was declared if 90% confidence intervals for the geometric mean ratio (GMR) for nicotinuric acid (NUA) Cmax fell within the pre-specified bounds of [0.7, 1.43].Results: The GMRs for NUA Cmax demonstrated similarity in the pharmacokinetics of NER uncoated 2 × 500 mg, NER coated 1 × 1000 mg, and NER coated 2 × 500 mg. Although less stringent comparability bounds were prespecified for the primary pharmacokinetic endpoint (i.e., Cmax of plasma NUA), inspection of the primary comparison of interest indicated that a hypothesis with more stringent bioequivalence bounds of [0.8, 1.25] would have been satisfied. The NUA Cmax for NER uncoated 1 × 1000 mg was approximately 40% higher than that seen for the other three treatments. In contrast, total urinary excretion of niacin and its metabolites, an approximate measure of bioavailability, was similar for all four treatments.Conclusion: The pharmacokinetic profile of the original NER uncoated formulation dosed as 2 × 500 mg was similar to the new film-coated formulation, NER coated, dosed as 1 × 1000 mg.

High radical oxygen scavenging (ROS) and antioxidant activity in Freeze‐dried Euterpe oleracea (OptiAcai) palm fruit pulp

The Euterpe oleracea palm fruit indigenous to Amazonia was tested for its ROS scavenging activity in multiple assay systems. Freeze-dried E. oleracea (OptiAcai, K2A LLC, Provo, UT) was found to significantly exceed ROS scavenging activity of any fruit or vegetable consumed in the United States. Total ORAC peroxyl radical scavenging was1026.9 μmoleTE/g, in addition to scavenging activity against the hydroxyl and peroxynitrite radicals. By comparison, ORAC of spray dried E. oleracea was only 61 μ moleTE/g. Superoxide scavenging activity was 1614, 3 times higher than any food. Significant major and minor polyphenolic compounds were identified by LC/MS/MS. Compared to other berries with ORAC values, total phenolic values were much lower suggesting that the phenolic compounds in E. oleracea are much stronger antioxidants than those of other berries. The content of condensed tannins (proanthocyanidins) was comparable to cacao, blueberry, and cranberry. The freeze-dried product showed a significant dose dependent inhibition of LPS-induced nitric oxide, increased macrophage engulfment on the macrophage phagocytosis assay, and significant inhibition of ROS formation in freshly purified human neutrophils even at dilutions of 1:100 and 1:1000. This freeze-dried palm fruit of E. oleracea deserves further study of its properties in vivo. Funding Source: AIBMR Life Sciences, Inc., Tacoma, Washington, and K2A LLC, Provo, Utah