Double-blind Placebo-controlled Pilot Study Research Articles

Transdermal application of H100 gel to the penile shaft in patients with Peyronie's disease infiltrates the tunica albuginea.

Treatment options for Peyronie's disease (PD) remain limited. Topical H100 gel, (Hybrid Medical, Edina, USA), which contains nicardipine, super oxide dismutase and emu oil showed safety and efficacy in a previous small double-blind placebo-controlled pilot study. The present study evaluates if topically applied H100 gel applied to the penile shaft infiltrates the tunica albuginea. Nicardipine is a key active ingredient in H100 and serves as a surrogate marker. Three men already scheduled to undergo a planned surgical procedure for PD applied commercially available H100 gel twice daily to the penile shaft for up to 30 days prior to the procedure. Tunica albuginea samples were obtained at surgery. Nicardipine evaluation was performed using isotope dilution technique via liquid-chromatograph-mass spectrometry (LCMS). All three patients tolerated H100 gel application without side effects. All three tunica albuginea specimens showed detectable nicardipine in the tunical tissue. Transdermal application of commercially available H100 gel is able to penetrate the tunica albuginea tissue and is detectable in men with acute and chronic PD. This finding may support the encouraging results found in the prior H100 pilot study.

Analysis of the Efficacy of Diet and Short-Term Probiotic Intervention on Depressive Symptoms in Patients after Bariatric Surgery: A Randomized Double-Blind Placebo Controlled Pilot Study

Analysis of the Efficacy of Diet and Short-Term Probiotic Intervention on Depressive Symptoms in Patients after Bariatric Surgery: A Randomized Double-Blind Placebo Controlled Pilot Study

A Double-Blind Placebo-Controlled Pilot Study of Topiramate in Manic Adolescents Treated with Olanzapine.

Objective: To conduct a pilot study to examine topiramate for the treatment of weight gain associated with olanzapine in manic adolescents with bipolar disorder. Methods: We conducted a 12-week double-blind randomized placebo-controlled pilot study of topiramate (300-400 mg/day) versus placebo in manic youth (ages 10-18 years) with bipolar disorder who were treated with olanzapine (10-20 mg/day). The primary outcome measure was gender- and weight-normed change in body mass index (BMI z-score). Results: Thirty manic adolescents were treated with olanzapine and were randomized to either topiramate (n = 16) or placebo (n = 14). There was a significantly greater increase in BMI z-scores in the placebo group (0.28 standard deviations [SDs]) compared with the topiramate group (0.10 SDs) when analyzed by longitudinal regression (p = 0.049). The placebo group had greater increases in raw BMI and weight (2.25 kg/m2 and 6.9 kg, respectively) compared with the topiramate (0.99 kg/m2 and 2.9 kg) group (p = 0.011 for BMI, p = 0.016 for weight). The most common adverse events in the topiramate group were headache (n = 7, 44%), gastrointestinal upset (n = 3, 19%), and muscle stiffness (n = 3, 19%). Conclusions: Topiramate may minimize the weight gain associated with olanzapine treatment in adolescents with bipolar disorder. Moreover, topiramate in combination with olanzapine was well tolerated. Larger studies that are adequately powered are necessary to determine the efficacy of topiramate for second-generation antipsychotic-related weight gain. Trial Registration: ClinicalTrials.gov Identifier number NCT00394095.

Study design and methods for the pilot study of muscadine grape extract supplement to improve fatigue among older adult cancer survivors (FOCUS) trial

IntroductionFatigue is a prevalent symptom among both cancer survivors and older adults. Negative consequences of fatigue include increased sedentary behavior, decreased physical activity and function, and lower quality of life. Few pharmacologic interventions improve fatigue. Our preclinical and clinical data show promising effects of a muscadine grape extract supplement (MGES) on oxidative stress, mitochondrial bioenergetics, the microbiome, and the symptom of fatigue. This pilot study seeks to translate these observations to cancer survivorship by testing the preliminary effect of MGE supplementation on older adult cancer survivors with self-reported fatigue. Materials and MethodsWe designed a double-blinded placebo-controlled pilot study to evaluate preliminary efficacy of MGE supplementation versus placebo on fatigue among older adult cancer survivors (aged ≥65 years) who report baseline fatigue. Sixty-four participants will be enrolled and randomized 1:1 to twice daily MGES (four tablets twice daily) versus placebo for 12 weeks. The primary outcome is change in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue score from baseline to 12 weeks. Secondary outcomes are change in self-reported physical function, physical fitness (6-min walk test), self-reported physical activity, global quality of life (QOL), and the Fried frailty index. Correlative biomarker assays will assess changes in 8-hydroxy-2 deoxyguanosine, peripheral blood mitochondrial function, inflammatory markers, and the gut microbiome. DiscussionThis pilot study builds on preclinical and clinical observations to estimate effects of MGE supplementation on fatigue, physical function, QOL, and biologic correlates in older adult cancer survivors.Trial registration #: CT.govNCT04495751; IND 152908.

Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study.

The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease. This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months). Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group. Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms. ClinicalTrial.gov, identifier: NCT03671785.

Effects of a Novel Amino Acid Formula on Nutritional and Metabolic Status, Anemia and Myocardial Function in Thrice-Weekly Hemodialysis Patients: Results of a Six-Month Randomized Double-Blind Placebo-Controlled Pilot Study.

(1) Background: Chronic Kidney Disease (CKD) induces metabolic derangement of amino acid (AA) kinetics, eliciting severe damage to the protein anabolism. This damage is further intensified by a significant loss of AAs through hemodialysis (HD), affecting all tissues with a high metabolic turnover, such as the myocardium and body muscle mass. (2) Aim: to illustrate the effects of a novel AA mixture in boosting mitochondrial energy production. (3) Methods: A strict selection of 164 dialysis patients was carried out, allowing us to finally identify 22 compliant patients who had not used any form of supplements over the previous year. The study design envisaged a 6-month randomized, double-blind trial for the comparison of two groups of hemodialysis patients: eleven patients (67.2 ± 9.5 years) received the novel AA mix (TRG), whilst the other eleven (68.2 10.5 years) were given a placebo mix that was indistinguishable from the treatment mix (PLG). (4) Results: Despite the 6-month observation period, the following were observed: maintenance of target hemoglobin values with a reduced need for erythropoiesis-stimulating agents in TRG > 36% compared to PLG (p < 0.02), improved phase angle (PhA) accompanied by an increase in muscle mass solely in the TRG group (p < 0.05), improved Left Ventricular Ejection Fraction (LVEF > 67%) in the TRG versus PLG group (p < 0.05) with early but marked signs of improved diastolic function. Increased sensitivity to insulin with greater control of glycemic levels in TRG versus PLG (p = 0.016). (5) Conclusions: the new AA mix seemed to be effective, showing a positive result on nutritional metabolism and cardiac performance, stable hemoglobin levels with the need for lower doses of erythropoietin (EPO), insulin increased cell sensitivity, better muscle metabolism with less loss of mass.

Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study

Functional iron deficiency facilitates allergy development and amplifies the symptom burden in people experiencing allergies. Previously we selectively delivered micronutrients to immune cells with β-lactoglobulin as carrier (holoBLG), resulting in immune resilience and allergy prevention. The clinical efficacy of a food for special medical purposes-lozenge containing β-lactoglobulin with iron, polyphenols, retinoic acid, and zinc (holoBLG lozenge) was assessed in allergic women. In a randomized, double-blind, placebo-controlled pilot study, grass- and/or birch pollen-allergic women (n= 51) were given holoBLG or placebo lozenges over 6 months. Before and after dietary supplementation, participants were nasally challenged and the blood was analyzed for immune and iron parameters. Daily symptoms, medications, pollen concentrations, and well-being were recorded by an electronic health application. Total nasal symptom score after nasal provocations improved by 42% in the holoBLG group versus 13% in the placebo group. The combined symptom medication score during the birch peak and entire season as well as the entire grass pollen season improved in allergic subjects supplemented with the holoBLG lozenge by 45%, 31%, and 40%, respectively, compared with the placebo arm. Participants ingesting the holoBLG lozenge had improved iron status with increased hematocrit values, decreased red cell distribution width, and higher iron levels in circulating CD14+ cells compared with the placebo group. Targeted micronutrition with the holoBLG lozenge seemed to be effective in elevating the labile iron levels in immune cells and reducing the symptom burden in allergic women in this pilot study. The underlying allergen-independent mechanism provides evidence that dietary nutritional supplementation of the immune system is one of the ways to combat atopy.

Exploring the Effect of Combined Transcranial and Intra-Oral Photobiomodulation Therapy Over a Four-Week Period on Physical and Cognitive Outcome Measures for People with Parkinson's Disease: A Randomized Double-Blind Placebo-Controlled Pilot Study.

Neuroprotection against Parkinson's disease degeneration by photobiomodulation has been reported in animal models but no true placebo-controlled human studies have been published. To understand if photobiomodulation therapy can produce clinically significant differences in physical performance measures in people with Parkinson's disease; and what frequency of treatment is necessary to initiate clinical change. In a participant and assessor-blinded, randomized, placebo-controlled pilot study, 22 participants received either sham and/or active laser photobiomodulation (904 nm, 60 mW/diode, 50 Hz) for 33 s to each of 21 points at the cranium and intra-orally, on one, two or three times/week for 4 weeks. Two treatment phases were separated by a 4-week wash-out (Phase 2). Upper and lower limb physical outcome measures were assessed before and after each treatment phase. The Montreal Cognitive Assessment was evaluated prior to treatment Phase 1, and at the end of treatment Phase 3. Montreal Cognitive Assessment remained stable between start and end of study. No measures demonstrated statistically significant changes. With regular treatment, the spiral (writing) test and the dynamic step test were most sensitive to change in a positive direction; and the 9-hole peg test demonstrated a minimum clinically important difference worthy of further investigation in a larger, adequately powered clinical trial. A placebo effect was noted. The results support the notion that combined transcranial and intra-oral photobiomodulation therapy needs to be applied at least 2 to 3 times per week for at least four weeks before some improvement in outcome measures becomes evident. Longer courses of treatment may be required.

A randomized double-blind placebo controlled pilot study of probiotics in adolescents with severe obesity.

The purpose of the study is to assess the effect of probiotic supplementation on gut microbiota and insulin resistance in adolescents with severe obesity. Through a randomized, double blind, placebo-controlled, 12-week pilot clinical trial, 15 adolescents with severe obesity received either an oral probiotic 'Visbiome®' (n = 8) or placebo (n = 7). Anthropometry, fasting glucose, insulin, hs-CRP and stool for microbiome and calprotectin were collected at baseline (week 0) and 12weeks after intervention. Among completers (n = 4 in each of the two groups), mean change in fasting glucose was significantly lower in the probiotic group (0 ± 4mg/dL) as compared to the placebo group (6.3 ± 1.7mg/dL) (p = 0.028). Gut microbial Firmicutes to Bacteroidetes (F/B) ratio had a greater decline from week 0 to week 12 in the probiotic group (mean 17.7 ± 25.1 to 2.39 ± 2.0, respectively) but was not statistically significant (p = 0.06) as compared to in the placebo group (mean 12.8 ± 18.2 to 6.9 ± 5.61, respectively) (p = 0.89). Weight and BMI (mean ± SD) trended to remain stable in the treatment group (-1.07 ± 6.1kg and -0.3 ± 2.2kg/m2 respectively) as compared to the placebo group (3.9 ± 5.1kg, 1.0 ± 1.6kg/m2) but was not significant (p = 0.12 for weight and 0.38 for BMI). No significant change in the fasting insulin, HOMA-IR, or serum and stool inflammatory markers were noted between the two groups (p > 0.05). One participant in the treatment arm reported adverse effects of gastrointestinal intolerance. Probiotic therapy with Visbiome® may improve the fasting glucose and possibly decrease the gut microbial F/B ratio as compared to placebo in adolescents with severe obesity. Future larger studies are required to confirm these findings.U.S. Clinical Trial Registry number: NCT03109587. The online version contains supplementary material available at 10.1007/s40200-021-00855-7.

Antioxidant Effect of Melatonin in Preterm Newborns.

Introduction Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. Objective The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin. Methods A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge. Results At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group (52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group (36.48 ± 33.85 pg/mL vs.89.97 ± 52.01 pg/mL). Conclusions Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.

Quercetin supplementation in non-alcoholic fatty liver disease

Purpose Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease which has become a public health concern, whose growing prevalence has been reported as around 33.9% in Iran. As oxidative stress plays a crucial role in the pathogenesis of NAFLD, antioxidant compounds such as quercetin could ameliorate the side effect of oxidative stress. The aim of the current study was to assess the effect of quercetin on lipid profile, liver enzymes and inflammatory indices in NAFLD patients. Design/methodology/approach In a randomized, double-blind, placebo-controlled trial conducted as a pilot study, 90 patients with NAFLD were supplemented with either a quercetin or a placebo capsule twice daily (500 mg) for 12 weeks. Both groups were advised to follow an energy-balanced diet with physical activity recommendations. Blood sample was obtained for laboratory parameters at baseline and the end of week 12. Findings At the end of the follow-up, quercetin group had significantly greater reduction in anthropometric parameters, cholesterol (−15 ± (−41, 0.00) in Q group versus −1± (−8, 2) in control group, p = 0.004), TG (−56.7 ± 22.7) in Q group versus −13.4 ± 27.7 in control group, p = 0.04), and tumor necrosis factor-α (TNF-α) (−49.5 ± (−99, 21) in Q group versus −5 ± (−21, 0.30) in the control group, p &lt; 0.0001) compared to the control group. However, changes in fatty liver grade, liver enzymes, as well as high density lipoprotein-cholesterol and high-sensitivity C-reactive protein were not significantly different between the two groups. Originality/value To the best of the authors’ knowledge, this was the first study which assessed the effect of quercetin supplementation on liver enzymes, lipid profile and inflammatory indices of NAFLD patients as a double-blind placebo-controlled pilot study.

Lycopene Reduces Skin Toxicity in Patients Treated with Panitumumab-Containing Therapy for Metastatic Colorectal Cancer – A Randomized Double-Blind Placebo-Controlled Pilot Study

Background: EGFR inhibition leads to the production of reactive oxygen metabolites, causing skin inflammatory reactions. Lycopene has an extreme antioxidant activity and, due to its hydrophobic structure, accumulates specifically in the skin. Methods: To assess lycopene effectiveness in reducing skin toxicity induced by panitumumab, 28 patients received lactolycopene or placebo in a phase-II PASTO study. Patients were evaluated at the beginning of each cycle and data were analyzed as the difference in mean grade of skin toxicity, frequency and duration of > G2 skin toxicity and frequency of tetracyclines administration. Lycopene, β-carotene and malondialdehyde plasma concentrations were analyzed to measure antioxidant consumption and oxidative stress. Findings: In the placebo group, ten out of 15 patients (66·67%), developed a > G2 skin toxicity, during 36 out of 92 cumulative cycles (39·1%), versus 3 out of 13 (23·08%), during 8 out of 64 cumulative cycles (12·5%) in the lactolycopene group. The time to the appearance of > G2 skin toxicity was different in the two groups (p= 0.0007 logrank test). Mean value of skin toxicity during treatment was 2·4 and 1·4 for placebo and lactolycopene group, respectively. Tetracyclines were administered for > G2 skin toxicity according to the protocol. Mean plasma concentration of lycopene and β-carotene decreased during treatment compared to day 0 (-141·94% and -157·22% respectively) in the placebo group, with a +109·36% mean malondialdehyde concentration increase. In contrast, in the lactolycopene group, mean plasma lycopene concentration increased during treatment (+94·18%), with a mean malondialdehyde concentration decrease (-68·83%) and a mean β-carotene concentration decrease (-105·5%) smaller than in the placebo group . Interpretation: Despite the limited number of patients, results clearly show lycopene effectiveness in reducing skin toxicity in patients treated with panitumumab. In our series lactolycopene administration was able to protect tissues from oxidative stress and to replenish antioxidants consumption. Trial Registration: registered in ClinicalTrials.gov (PaSTo – Clinicaltrials.gov: NCT 03167268) Funding Statement: AMOlavitaONLUS, Indena Spa. Declaration of Interests: MM1 is the vice-president and MP the treasurer of AMOlavitaONLUS. AMOlavitaONLUS is the sole owner and it holds all the ownership rights on the international patent application entitled “Use of carotenoid derivatives to reduce the toxicity and increase the efficacy of antiEGFR antitumor treatments” (N°PCT/IB2018/050229). MM1 and MP are exclusively inventors of the patent and they have no ownership right on the patent. Indena Spa, who supplied free of charge lactolycopene for the Pasto Clinical Trial, is not the owner of the patent for lactolycopene production. All other authors declare no competing interest. Ethics Approval Statement: The protocol was approved by the ethics committees of all participating institutions. Written informed consent was obtained from all patients.

Influence of energy drinks on acute hemodynamic parameters in young healthy adults: a randomized double-blind placebo-controlled crossover pilot study

Influence of energy drinks on acute hemodynamic parameters in young healthy adults: a randomized double-blind placebo-controlled crossover pilot study

Ameliorating Effects of Delphinol&amp;#174;, Anthocyanin Standardized Maqui Berry Extract, on Skin Brightness and Redness in Japanese Females: A Randomized Double-Blind Placebo-Controlled Pilot Study

Maqui berries are wildly grown or cultivated in the Patagonian region in Chile. The berries contain large amounts of anthocyanins, especially delphinidin glycosides, which are strong anti-oxidants. We previously reported that standardized maqui berry extract, which contained lots of anthocyanins, has ameliorative effects against dry eyes and visible light-induced photoreceptor cell damage. However, the influence of maqui berry extract on the human skin has not been evaluated even though many skin troubles are related to active oxygen species. Therefore, we conducted a randomized double-blind placebo-controlled pilot study with Delphinol®, a maqui berry extract standardized for anthocyanins, especially delphinidins and cyanidins, in healthy Japanese female subjects. Capsules containing Delphinol® (60 mg) or placebo were orally administered to subjects aged 27 to 57 years old for eight weeks. Skin conditions [pigmentation, redness, skin tone, wrinkles, texture, oil content, water content, trans epidermal water loss (TEWL), collagen score, dermal thickness, and elasticity] were measured before and after intervention. In the Delphinol® group, the saturation significantly increased after eight weeks and reddish spots significantly decreased after four weeks of intake. The collagen score, which decreases with age, slightly increased with age by Delphinol® ingestion for eight weeks. Thus, the anthocyanin-standardized maqui berry extract Delphinol® increased skin brightness and collagen content, and improved facial skin redness. This study suggests that the daily oral intake of maqui berry extract can help maintain a healthy facial condition.

Ubiquinol Improves Endothelial Function in Patients with Heart Failure with Reduced Ejection Fraction: A Single-Center, Randomized Double-Blind Placebo-Controlled Crossover Pilot Study

Endothelial dysfunction is reportedly associated with worse outcomes in patients with chronic heart failure. Ubiquinol is a reduced form of coenzyme Q10 (CoQ10) that may improve endothelial function. We assessed the hypothesis that ubiquinol improves peripheral endothelial function in patients with heart failure with reduced ejection fraction (HFrEF). In this randomized, double-blind, placebo-controlled, crossover pilot study, 14 patients with stable HFrEF were randomly and blindly allocated to ubiquinol 400mg/day or placebo for 3months. After a 1-month washout period, patients were crossed over to the alternative treatment. Before and after each treatment, we assessed peripheral endothelial function using the reactive hyperemia index (RHI) and analyzed it using the natural logarithm of RHI (LnRHI). Peripheral endothelial function as assessed by LnRHI tended to improve with ubiquinol 400mg/day for 3months (p = 0.076). Original RHI values were also compared, and RHI significantly improved with ubiquinol treatment (pre-RHI 1.57 [interquartile range (IQR) 1.39-1.80], post-RHI 1.74 [IQR 1.63-2.02], p = 0.026), but not with placebo (pre-RHI 1.67 [IQR 1.53-1.85], post-RHI 1.51 [IQR 1.39-2.11], p = 0.198). Ubiquinol 400mg/day for 3months led to significant improvement in peripheral endothelial function in patients with HFrEF. Ubiquinol may be a therapeutic option for individuals with HFrEF. Large-scale randomized controlled trials of CoQ10 supplementation in patients with HFrEF are needed. Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000012604.

Effect of probiotics on the occurrence of nutrition absorption capacities in healthy children: a randomized double-blinded placebo-controlled pilot study.

Recent advances in the translational research showed that dietary nutrients have critical importance to the microbioma balance in the gastrointestinal tract. Therefore, the alteration of the intestinal microbiota in order to achieve, restore, and maintain favorable balance in the ecosystem, and the activity of microorganisms present in the gastrointestinal tract is necessary for the improved health condition of the host. The objective of this translational study was to evaluate, in a pediatric population, the efficacy and safety of prophylactic probiotics for a better nutritional absorption capacity in the view to enhance their overall health and immunity. A total of 40 pediatric patients between the ages of 14 and 18 years were enrolled in the study and divided under two categories (treated/active group and placebo group). Three-time points clinical evaluations were performed: a baseline assessment (Time 0), a second evaluation at 5 weeks after the start of probiotic use (Time 1), and a final evaluation at the timeline after 10 weeks (Time 2). In the initial phase of the study, the recruited subjects underwent a panel of initial T0 clinical tests. For each of the patients, a blood sample was taken in order to evaluate the following biochemical measurements: Vitamin D, Vitamin A, Calcium, Zinc, and Iron. Moreover, an initial nutritional evaluation was carried out through which the nutritionist estimated the body composition of the subject (weight and body mass index), the caloric needs and dietary behaviour of each recruited patient. Eligible participants were randomized into placebo (n= 20) or treated/active (n= 20) treatment conditions by random allocation using a computerized random number generator, ensuring all investigators remained blind to the treatment distribution. The data were compared within and between groups using statistical methods. The results confirmed that the probiotic supplementation was effective in increasing the overall blood biomarkers levels of vitamins, calcium, and mineral absorption from baseline to 10 weeks of treatment, compared with the placebo. Probiotics may be suggested as supplements to improve biomarkers serum concentration if administered for a period of at least ≥ 5 weeks. However, further studies are required for optimal recommendations in patient treatment.

167. Assessment of the efficacy of teriparatide (Forteo) in patients undergoing posterolateral lumbar spinal fusion: a double-blinded randomized pilot study

BACKGROUND CONTEXT Lumbar spinal fusion is an increasingly common procedure for treating degenerative diseases of the lumbar spine. Non-solid fusion, or pseudarthrosis, at one year is a common complication associated with poor clinical outcomes and need for revision surgery. The risk of pseudarthrosis depends on the number of levels fused, the fusion material, and patient risk factors (osteoporosis, smoking, diabetes, etc.). Although there are multiple options for bone graft and osteoinductive materials, all have their benefits, side-effects and cost. Teriparatide is an injectable recombinant analog of parathyroid hormone that has been well-studied in its treatment of osteoporosis. However, no clinical studies of its effect on spinal fusion in humans have been published to date. PURPOSE To analyze the effect of teriparatide treatment on posterolateral spinal fusion in adults with degenerative diseases of the lumbar spine. STUDY DESIGN/SETTING Multicenter prospective double-blinded randomized study. PATIENT SAMPLE 60-90 year-olds with degenerative scoliosis, spondylolisthesis, or spondylosis at two medical centers undergoing instrumented posterolateral instrumented fusion >2levels. Use of BMP was excluded. OUTCOME MEASURES Pseudoarthrosis, screw loosening, PJK by CT. VAS, ODI, and Eq5D. METHODS Prospective randomized double-blind placebo-controlled pilot study performed at two large academic centers, UCSF and McGill University (Montreal). Included patients were aged 60-90 years with degenerative lumbar disease who were scheduled to undergo two-level or greater posterolateral lumbar spinal fusion. Patients were randomized in a 2:1 (Forteo:Placebo) manner. Patient were dosed 2 weeks pre-op and 10 weeks post-op. Patient derived outcomes were collected pre-op, 3, 6, 9, and 12 months. Fusions at 1 year were analyzed by helical CT. RESULTS A total of 36 patients completed the study. 58.3% (n=21) received teriparatide. 42.8% (n=9) reported an adverse event. Fusion rate of all patients was 47.2% (n=17); the remaining 52.8% (n=19) demonstrated pseudoarthrosis at 1 year. Fourty-seven percent of patients receiving teriparatide had a pseudoarthrosis, while 60% of placebo had a pseudoarthrosis. VAS, ODI, and Eq5D improved in all groups but no significant difference was found between groups. CONCLUSIONS Teriparatide appears to provide minimal benefit of avoiding pseudoarthroses in 60-90 year-olds undergoing thoracolumbar fusions. Teriparatide appears to have a fairly safe side effect profile. Further larger scale studies are warranted, possibly with the addition of BMP and/or bisphosphonates. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.

Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus (T2DM)1. The gut microbiota is considered as a new key contributor involved in the onset of obesity-related disorders2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated T2DM, or hypertension3–8. As the administration of A.muciniphila has never been investigated in humans, we conducted a randomized double-blind placebo-controlled pilot study in overweight/obese insulin resistant volunteers, 40 were enroled and 32 completed the trial. The primary endpoints were on safety, tolerability and metabolic parameters (i.e., insulin resistance, circulating lipids, visceral adiposity, body mass). The secondary outcomes were the gut barrier function (i.e., plasma lipopolysacharrides (LPS) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 bacteria either alive or pasteurized A.muciniphila for 3 months was safe and well tolerated. Compared to the Placebo, pasteurized A.muciniphila improved insulin sensitivity (+28.62±7.02%, P=0.002), reduced insulinemia (-34.08±7.12%, P=0.006) and plasma total cholesterol (-8.68±2.38%, P=0.02). Pasteurized A.muciniphila supplementation slightly decreased body weight (-2.27±0.92kg, P=0.091) as compared to the Placebo group, and fat mass (-1.37±0.82kg, P=0.092) and hip circumference (-2.63±1.14cm, P = 0.091) as compared to baseline. After 3 months of supplementation, A.muciniphila reduced the levels of relevant blood markers of liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (NCT02637115) shows that the intervention was safe and well-tolerated and that the supplementation with A.muciniphila improves several metabolic paramaters.

Pediococcus Acidilactici NRRL B-50517 as a Safe Probiotic for Regulation of Weight Related Pro-inflammatory Cytokines: A Double-blind Placebo-controlled Pilot Study (P21-026-19)

ObjectivesDevelopment of a probiotic P. acidilactici NRRL B-50517 that resists to high temperature (up to 85°C), stomach acids, and air. Clinic evaluation of P. acidilactici NRRL B-50517 as a safe probiotic for regulation of weight related pro-inflammatory cytokines. MethodsSurvival studies were conducted by incubating P. acidilactici NRRL B-50517 in either liquid MRS broth, pH1.5 at 85°C overnight, or in dried powder at 85°C for 5–10 minutes. Healthy volunters were randomly assigned two capsules of placebo or Pediococcus probiotics (4 billion CFU) daily for three months. Biweekly phone interviews with 30 participants were performed to ensure daily dosage administration, and to collect the results of the questionnaire related to 6 categories of gut functions. Percent body fat measurements and serum were collected upon study initiation and completion. Serum was processed for cytokine analysis by multiplex ELISA assays. ResultsP. acidilactici NRRL B-50,517 survived at 85°C and pH 1.5 in MRS broth and dried powder forms. No statistical significantly changes of gut functions between the placebo group and the probiotic group in appetite: t-value 1.6808, p-value 0.1313; energy level: t-value 0.7508. p-value 0.5003; bowel movement: t-value 0.3348. p-value 0.7464; stool quality: t-value 0.6929, p-value 0.5080; bloating: t-value 2.0583. p-value 0.0736; gas t-value: 1.9560, p-value 0.0875. On average, the probiotic lost 0.86% ± 0.42% body fat whereas the control group gained 0.28% ± 0.19, P = 0.0264. Pro-inflammaroty IL-6 ratios differed by 0.61 ± 0.22 and 3.06 ± 0.87 in the probiotic and control groups, respectively (P = 0.0295); pro-inflammatory IL23 ratio was 0.65 ± 0.14 in the probiotic and 1.71 ± 0.38 in the control group, P = 0.0068. ConclusionsNovel P. acidilactici NRRL B-50,517 is safe for human consumption and may be useful in reducing body fat and pro-inflammatory markers. Funding SourcesTEDCO, Maryland.

Probiotics Efficacy on Oxidative Stress Values in Inflammatory Bowel Disease: A Randomized Double-Blinded Placebo-Controlled Pilot Study.

Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are described as a chronic inflammation of the small intestine and colon, caused by a dysregulated immune response to host intestinal microbiota in genetically susceptible subjects. The aim of this study was to compare probiotic therapy versus placebo in Oxidative Stress Values and clinical features in patients affected by IBD. Forty (40) patients previously diagnosed for IBD were recruited and randomized to receive probiotics (test group, n=20) or placebo (control group, n=20) administered for 90 days. Subjects in both the groups were assessed for overall oxidant ability (d-ROMs test) and for the antioxidant response (BAP test): data were reported at baseline, after 1 and 3 months. Additional data from anamnesis and haematological investigation were also reported during the study. d-ROM assay clearly showed that the values observed in the test group were significantly improved, leading to oxidative stress values which are not pathological. The test group showed increasing BAP values, thus confirming the overall improvements of patients 'health following administration of probiotics. Oral administration of the specific probiotics demonstrated its efficacy and safety on patients affected by IBD.