Inflammatory Bowel Disease Trials Research Articles

2019 Harry Shwachman Award

2019 Harry Shwachman Award

Trends and Characteristics of Clinical Trials Participation for Inflammatory Bowel Disease in the United States: A Report From IBD Partners.

Background and AimsThere are currently several recruitment challenges in randomized controlled trials (RCTs) for inflammatory bowel disease (IBD), which prolong the drug approval process and affect the generalizability of study results. The purpose of this study is to characterize individuals who participate in IBD RCTs and identify factors that could influence future recruitment strategies.MethodsWe performed a cross-sectional study within the IBD Partners cohort comparing patients with current or prior participation in an RCT of medical therapy for IBD to those without any RCT participation. Bivariate statistics were used to compare RCT participation by IBD subtype and by other demographic and disease characteristics, and predictive modeling was used to identify factors predictive of RCT participation. We calculated the percent of the cohort that participated in an RCT during each calendar year from 2011 to 2018 and accessed Clinicaltrials.gov to determine the number of active RCTs for IBD therapies per year during that same period.ResultsA total of 14,747 patients with IBD were included in the analysis and 1116 (7.6%) reported RCT participation at any time. Demographic factors predictive of RCT participation included following at an academic institution [odds ratio (OR) = 1.8; 95% confidence interval (CI) 1.51–2.04) and age 36–75 (OR = 1.7; 95% CI 1.46–1.92). Patients with Crohn’s disease were more likely to participate than those with ulcerative colitis (OR = 1.5; 95% CI 1.35–1.77). Patients with more severe disease were more likely to participate, including those with prior IBD-related hospitalization (OR = 2.6; 95% CI 2.19–2.99), IBD-related surgery (OR = 2.5; 95% CI 2.24–2.87), biologic exposure (OR = 3.2; 95% CI 2.76–3.65), and “Poor” or worse quality of life (OR = 1.7; 95% CI 1.45–1.93). Steroid-free remission was associated with a lower likelihood of RCT participation (OR = 0.6; 95% CI 0.53–0.70). Although the number of active RCTs for IBD more than doubled between 2011 and 2018, RCT participation rates during that same time period decreased from 1.1% to 0.7% of the cohort.ConclusionsRCT participation declined within this cohort. Groups underrepresented in RCTs for IBD included younger patients, patients followed in community settings, and patients with more mild disease. The non-RCT group had mean disease activity scores that did not meet remission thresholds, demonstrating populations in need of alternate therapies for whom clinical trials could be an option. Given anti-tumor necrosis factor (TNF) exposure rates in this national cohort, studies should focus on anti-TNF failure populations. Investigators should make every effort to offer RCTs to all patients and network with community providers to increase awareness of RCTs.

Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases.

Serotonin, also known as 5-hydroxytryptamine (5-HT) is a signaling mediator that regulates emotion, behavior, and cognition. Previous studies have focused more on the roles of 5-HT in the central nervous system (CNS). However, 5-HT also shares a strong relationship with the pathological cases of tumor, inflammation, and pathogen infection. 5-HT participates in tumor cell migration, metastatic dissemination, and angiogenesis. In addition, 5-HT affects immune regulation via different 5-HT receptors (5-HTRs) expressed immune cells, including both innate and adaptive immune system. Recently, drugs targeting at 5-HT signaling were tested to be beneficial in mouse models and clinical trials of multiple sclerosis (MS) and inflammatory bowel disease (IBD). Thus, it is reasonable to assume that 5-HT participates in the pathogenesis of autoimmune diseases. However, the underlying mechanism by 5-HT modulates the development of autoimmune diseases has not been fully understood. Based on our previous studies and pertinent literature, we provide circumstantial evidence for an essential role of 5-HT, especially the regulation of 5-HT on immune cells in the pathogenesis of autoimmune diseases, which may provide a new point cut for the treatment of autoimmune diseases.

PLACEBO USE IN THE CONTEXT OF INFLAMMATORY BOWEL DISEASE CLINICAL TRIALS.

Inflammatory bowel disease comprises two distinct conditions - Crohn's disease and ulcerative colitis - which can be treated with immunomodulators. A non-neglectable proportion of these patients will need biologic therapy, and many patients under biologic treatment will experience either primary or secondary failure. As a consequence, clinical trials evaluating new therapeutic alternatives are being developed. These trials share common features, such as being controlled with placebo. Placebo use in clinical trials is a matter of intense debate. Those who support placebo use highlight the methodologic advantages placebo-controlled trials have. Those against placebo use argue that it would be against ethical principles in clinical research to expose a patient to placebo when a valid therapeutic alternative exists. In this review, we summarize the existing arguments for and against the use of placebo in the context of inflammatory bowel disease research. We finally suggest that it is very likely that in the near future inflammatory bowel disease trials will no longer be controlled with a placebo arm, but instead they will be non-inferiority trials with an active comparator.

P070 TRENDS AND CHARACTERISTICS OF CLINICAL TRIALS PARTICIPATION IN THE IBD PARTNERS COHORT

Abstract Background and Aims There are currently several recruitment challenges in randomized controlled trials (RCT) for inflammatory bowel disease (IBD) which prolong the drug approval process and affect the generalizability of study results. The purpose of this study is to characterize individuals who participate in IBD RCTs and identify factors which could influence future recruitment strategies. Methods We performed a cross-sectional study within the IBD Partners cohort comparing patients with current or prior participation in an interventional randomized controlled trial (RCT) of a medical therapy for IBD to those without any RCT participation. Bivariate statistics were used to compare RCT participation by IBD subtype and by other demographic and disease characteristics, and predictive modeling was used to identify factors predictive of RCT participation. We calculated the percent of the cohort that participated an in RCT during each calendar year from 2011–2018 and Clinicaltrials.gov was accessed to determine the number of active RCTs for IBD therapies per year during that same period. Results A total of 14,747 patients with IBD were included in the analysis and 1,116 (7.6%) reported RCT participation at any time. Demographic factors predictive of RCT participation (Table 1) included following at an academic institution (OR=1.8; 95%CI: 1.51–2.04) and age 36–75 (OR=1.6; 95%CI: 1.43–1.87). Patients with Crohn’s disease (CD) were more likely to participate than those with ulcerative colitis (UC) (OR=1.5; 95%CI: 1.35–1.77). Patients with more severe disease were more likely to participate, including those with prior IBD-related hospitalization (OR=2.6; 95%CI: 2.19–2.99), IBD-related surgery (OR=2.5; 95%CI: 2.24–2.87), biologic exposure (OR=3.2; 95%CI: 2.76–3.65), and “Poor” or worse quality of life (OR=1.7; 95%CI: 1.45–1.93). Steroid-free remission was associated with lower likelihood of RCT participation (OR=0.6; 95%CI: 0.53–0.70). While the number of active RCTs for IBD more than doubled between 2011 and 2018, RCT participation rates during that same time period decreased from 1.1% to 0.7% of the cohort (Figure 1). Conclusions RCT participation rates declined within this cohort between 2011–2018. Groups underrepresented in RCTs for IBD included younger patients, patients followed in community settings, and patients with more mild disease. The non-RCT group had mean sCDAI and SCCAI scores that did not meet remission thresholds, demonstrating populations in need of alternate therapies for whom clinical trials could be an option. Given anti-TNF exposure rates in this national cohort, studies should focus on anti-TNF failure populations. Investigators should make every effort to offer RCTs to all patients and network with community providers to increase awareness of RCTs.

P427 A hybrid approach of handling missing data in inflammatory bowel disease (IBD) trials: results from VISIBLE 1 and VARSITY

Abstract Background Missing data is common in IBD trials. Depending on the volume and nature of missing data, it can reduce statistical power for detecting treatment difference, introduce potential bias and invalidate conclusions. Non-responder imputation (NRI), where patients (patients) with missing data are considered treatment failures, is widely used to handle missing data for dichotomous efficacy endpoints in IBD trials. However, it does not consider the mechanisms leading to missing data and can potentially underestimate the treatment effect. We proposed a hybrid (HI) approach combining NRI and multiple imputation (MI) as an alternative to NRI in the analyses of two phase 3 trials of vedolizumab (VDZ) in patients with moderate-to-severe UC – VISIBLE 11 and VARSITY2. Methods VISIBLE 1 and VARSITY assessed efficacy using dichotomous endpoints based on complete Mayo score. Full methodologies reported previously.1,2 Our proposed HI approach is aimed at imputing missing Mayo scores, instead of imputing the missing dichotomous efficacy endpoint. To assess the impact of dropouts for different missing data mechanisms (categorised as ‘missing not at random [MNAR]’ and ‘missing at random [MAR]’, HI was implemented as a potential sensitivity analysis, where dropouts owing to safety or lack of efficacy were imputed using NRI (assuming MNAR) and other missing data were imputed using MI (assuming MAR). For MI, each component of the Mayo score was imputed via a multivariate stepwise approach using a fully conditional specification ordinal logistic method. Missing baseline scores were imputed using baseline characteristics data. Missing scores from each subsequent visit were imputed using all previous visits in a stepwise fashion. Fifty imputation datasets were computed for each component of Mayo score. The complete Mayo score and relevant efficacy endpoints were derived subsequently. The analysis was performed within each imputed dataset to determine treatment difference, 95% CI and p-value, which were then combined via Rubin’s rules3. Results Tables 1 and 2 show a comparison of efficacy in the two studies using the primary NRI analysis vs. the alternative HI approach for handling missing data. Conclusion HI and NRI approaches can provide consistent efficacy analyses in IBD trials. The HI approach can serve as a useful sensitivity analysis to assess the impact of dropouts under different missing data mechanisms and evaluate the robustness of efficacy conclusions. Reference

Phase I, II and III Trials in Inflammatory Bowel Diseases: A Practical Guide for the Non-specialist.

In the last few decades several new molecules have been developed in the field of inflammatory bowel diseases. However, the process that leads to the approval and use of a new drug is very long, expensive and complex, consisting of various phases. There is a pre-clinical phase that is performed on animals and a clinical phase that is directed to humans. Each research phase aims to evaluate different aspects of the drug and involves a specific target group of subjects. In addition, many aspects must be considered in the evaluation of a clinical trial: randomization, presence of a control group, blind design, type of data analysis performed, and patient stratification. The objective of this review is to provide an overview of the clinical trial phases of a new drug in order to better understand and interpret their results.

Diagnosis and natural history of preclinical and early inflammatory bowel disease.

Inflammatory bowel disease is a chronic and progressive disorder of the gastrointestinal tract. A relevant proportion of patients develop complicated lesions, defined as strictures, fistulas and/or abscesses already at diagnosis, and this proportion increases over time. The preclinical phase defines the period of time from the appearance of the first immune disturbances until the development of overt disease, and it may be present months to years before the diagnosis. Multiple biomarkers (e.g., C-reactive protein, interleukin-6, fecal calprotectin) and cellular mechanisms (e.g., complement cascade, lysosomes, innate immunity, and glycosaminoglycan metabolism) are already altered during this period. Research in this area allows the description of the initial immune disturbances that may identify potential targets and lead to the development of new drug therapies. During this period, different interventions in high-risk individuals, including drugs or environmental factors, will open the possibility of innovative strategies focused on the reduction of complications, or even prevention trials for inflammatory bowel disease. Here, we review the most relevant findings regarding the characteristics, prevalence and biomarkers associated with preclinical disease, along with their possible use in our future clinical practice.

Listening to the Patient: Improving the Design and Conduct of Clinical Trials in Inflammatory Bowel Diseases.

Lay Summary There is an urgent need for new treatments for inflammatory bowel diseases, but it’s hard to enroll the large number of patients needed for clinical trials. Making trials more patient-friendly by giving patients a voice would help solve this problem.

Barriers and Facilitators in Conducting Clinical Trials in Inflammatory Bowel Disease: A Monocentric Italian Survey

Barriers and Facilitators in Conducting Clinical Trials in Inflammatory Bowel Disease: A Monocentric Italian Survey

Preferences of Adult Patients With Inflammatory Bowel Disease for Attributes of Clinical Trials: Evidence From a Choice-Based Conjoint Analysis.

Clinical trial recruitment is the rate-limiting step in developing new treatments. To understand inflammatory bowel disease (IBD) patient recruitment, we investigated two questions: Do changes in clinical trial attributes, like monetary compensation, influence recruitment rates, and does this influence differ across subgroups? We answered these questions through a conjoint survey of 949 adult IBD patients. Recruitment rates are influenced by trial attributes: small but significant increases are predicted with lower placebo rates, reduced number of endoscopies, less time commitment, open label extension, and increased involvement of participant's primary GI physician. A much stronger effect was found with increased monetary compensation. Latent class analysis indicated three patient subgroups: some patients quite willing to participate in IBD trials, some quite reluctant, and others who can be persuaded. The persuadable group is quite sensitive to monetary compensation, and payments up to US$2,000 for a 1-year study could significantly increase recruitment rates for IBD clinical trials. This innovative study provides researchers with a framework for predicting recruitment rates for different IBD clinical trials.

861 Mind the Gap: A Comparison of the Randomized Clinical Trial Efficacy and Real World Effectiveness of Tofacitinib for the Treatment of Inflammatory Bowel Disease

INTRODUCTION: Randomized clinical trials (RCTs) represent the gold standard for clinical evidence. However, they have also raised concerns over generalizability due to unrealistic patient selection and endpoints. Real-world data (RWD) is receiving growing interest from the FDA as a complementary source of evidence. However, the suitability of these data for RCT-grade evidence and best practices in their use remain unclear. Here we compare the real-world effectiveness of Tofacitinib with efficacy assessed by RCTs of Inflammatory Bowel Disease (IBD). METHODS: Electronic health records (EHR) at the University of California San Francisco (UCSF) were reviewed for IBD patients prescribed Tofacitinib following a pre-protocol. The primary outcome was drug effectiveness measured by continued use and by RCT endpoints. Secondary outcomes assessed the completeness of RWD to measure RCT endpoints and the number of patients meeting RCT inclusion criteria. RESULTS: 68 Ulcerative Colitis (UC) and 18 Crohn’s Disease (CD) patients received Tofacitinib (Figure 1). Most of the data needed to calculate the RCT endpoints was available in the EHR (77% and 91%) with the remainder imputed. The baseline characteristics of the UCSF and trial cohorts were similar, except for greater disease duration and 100% TNFi failure in UCSF patients (Table 1). However, 0% of the real-world UC cohort met the RCT inclusion criteria (Table 2). The rate of continued treatment at 1 year was greater than 50% irrespective of disease subtype. Time-to-treatment-failure curves were nearly identical for UC and CD, with all drop-off occurring within the first 6 months. This rate of continued treatment in practice was significantly greater than the RCT primary endpoint and least stringent secondary endpoint (P-values 0.003 and 0.08) for UC, and for CD (P-value 0.02). However, the rates of meeting the primary endpoint for both subtypes using the Mayo score and CDAI were identical (P-values 0.5 and 1.0). CONCLUSION: Routinely collected data is sufficiently detailed to measure IBD trial endpoints. Analysis of RWD reproduced Tofacitinib efficacy measured by RCTs, despite trial selection criteria excluding most UCSF patients. However, real-world use patterns indicate much greater treatment durability than that suggested by trial endpoints, likely related to different treatment failure thresholds used in clinical care. These results support a role for JAK inhibition in CD, and overall highlight the value of real-world evidence to complement that obtained by RCTs.

Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats

BackgroundWe focused on the therapeutic effects of the stable gastric pentadecapeptide BPC 157 in spinal cord injury using a rat model. BPC 157, of which the LD1 has not been achieved, has been implemented as an anti-ulcer peptide in inflammatory bowel disease trials and recently in a multiple sclerosis trial. In animals, BPC 157 has an anti-inflammatory effect and therapeutic effects in functional recovery and the rescue of somatosensory neurons in the sciatic nerve after transection, upon brain injury after concussive trauma, and in severe encephalopathies. Additionally, BPC 157 affects various molecular pathways.MethodsTherefore, BPC 157 therapy was administered by a one-time intraperitoneal injection (BPC 157 (200 or 2 μg/kg) or 0.9% NaCl (5 ml/kg)) 10 min after injury. The injury procedure involved laminectomy (level L2-L3) and a 60-s compression (neurosurgical piston (60–66 g) of the exposed dural sac of the sacrocaudal spinal cord). Assessments were performed at 1, 4, 7, 15, 30, 90, 180, and 360 days after injury.ResultsAll of the injured rats that received BPC 157 exhibited consistent clinical improvement, increasingly better motor function of the tail, no autotomy, and resolved spasticity by day 15. BPC 157 application largely counteracted changes at the microscopic level, including the formation of vacuoles and the loss of axons in the white matter, the formation of edema and the loss of motoneurons in the gray matter, and a decreased number of large myelinated axons in the rat caudal nerve from day 7. EMG recordings showed a markedly lower motor unit potential in the tail muscle.ConclusionAxonal and neuronal necrosis, demyelination, and cyst formation were counteracted. The functional rescue provided by BPC 157 after spinal cord injury implies that BPC 157 therapy can impact all stages of the secondary injury phase.

Pentadecapeptide BPC 157, in Clinical Trials as a Therapy for Inflammatory Bowel Disease (PL14736), Is Effective in the Healing of Colocutaneous Fistulas in Rats: Role of the Nitric Oxide-System

We focused on the therapeutic effect of the stable gastric pentadecapeptide BPC 157 and how its action is related to nitric oxide (NO) in persistent colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin defect of 5 mm); this peptide has been shown to be safe in clinical trials for inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy. BPC 157 (10 μg/kg, 10 ng/kg) was applied i) in drinking water until the animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii) once daily intraperitoneally (first application 30 min following surgery, last 24 h before sacrifice) alone or with NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg), L-arginine (200 mg/kg), and their combinations. Sulphasalazine (50 mg/kg) and 6-α-methylprednisolone (1 mg/kg) were given once daily intraperitoneally. BPC 157 accelerated parenterally or perorally the healing of colonic and skin defect, leading to the suitable closure of the fistula, macro/microscopically, biomechanically, and functionally (larger water volume sustained without fistula leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (l-NAME groups). l-Arginine was effective only with blunted NO generation (l-NAME + l-arginine groups) but not without (l-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (l-NAME + BPC 157 groups) and with NO substrate (l-arginine + BPC 157 groups) as well as l-NAME and l-arginine co-administration (L-NAME + l-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect.

Are We Ready to Include Prognostic Factors in Inflammatory Bowel Disease Trials?

Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by periodic episodes of flares and remission. Treatment is aimed at healing the bowel, to ultimately decrease hospitalization rates, need for surgeries and overall disability. In more recent years, treatment has transitioned from a reactive approach to a more proactive approach focusing on treating disease earlier and preventing complications. The challenge lies in identifying patients who need more intensive treatment early and trying to determine who will respond to which medications. Biomarkers and clinical activity scoring systems can be used to help guide treatment decisions. However, IBDs are very heterogeneous and the significance of these biomarkers can be difficult to discern on an individual basis. Recently, prognostic tools have been developed to aid in determining a patient's prognosis as well as their likelihood to respond to different therapies. Despite this progress, clinical trials have not routinely adopted this approach in their study design. Tools for stratification of disease severity and to personalize treatment choices have the potential to improve our studies both by enriching the patient population and further guiding clinical decision making in practice. This review aims to discuss biomarkers, current prognosticating tools, tools that determine response to therapy and how incorporating these into clinical trials will be beneficial.

Particularities of IBD Trials in Children.

Pediatric inflammatory bowel diseases (IBD) are similar to the adult-onset type in many aspects, including the necessity of high-quality randomized controlled trials. However, recruiting children into clinical trials is conceptually more challenging than in adults. Furthermore, the long delay between adult and pediatric approval of new drugs leads not only to the unbearable extensive use of these drugs as off-label without appropriate dosing and safety data but also to more challenges when eventually the pediatric trial is performed. This review offers possible solutions to age-specific pitfalls in performing trials in pediatric IBD. Many of the challenges could be adequately addressed by accepting full extrapolation of efficacy from adult trials. This is advisable if small pharmacokinetics/ pharmacodynamics (PK/PD) studies show similarity to adult data. Then, pediatric trials can focus on dosing and safety while avoiding the controversial use of placebo. Judicious use of non-invasive activity scores and biomarkers, providing immediate and effective treatment in active disease and ensuring equipoise of treatments both within and outside the trial are the mainstay of a feasible trial in children. The recent trend of including adolescents in adult phase-3 trials addresses some obstacles but introduces others. Acknowledging and addressing these age-specific challenges would facilitate pediatric drug development in IBD.

Nuclear Receptors Regulate Intestinal Inflammation in the Context of IBD.

Gastrointestinal (GI) homeostasis is strongly dependent on nuclear receptor (NR) functions. They play a variety of roles ranging from nutrient uptake, sensing of microbial metabolites, regulation of epithelial intestinal cell integrity to shaping of the intestinal immune cell repertoire. Several NRs are associated with GI pathologies; therefore, systematic analysis of NR biology, the underlying molecular mechanisms, and regulation of target genes can be expected to help greatly in uncovering the course of GI diseases. Recently, an increasing number of NRs has been validated as potential drug targets for therapeutic intervention in patients with inflammatory bowel disease (IBD). Besides the classical glucocorticoids, especially PPARγ, VDR, or PXR-selective ligands are currently being tested with promising results in clinical IBD trials. Also, several pre-clinical animal studies are being performed with NRs. This review focuses on the complex biology of NRs and their context-dependent anti- or pro-inflammatory activities in the regulation of gastrointestinal barrier with special attention to NRs already pharmacologically targeted in clinic and pre-clinical IBD treatment regimens.

Fecal microbiota transplantation: great potential with many challenges.

In January of 2019, Samuel P. Costello and colleagues published a wonderfully executed, double blind placebo-controlled trial on fecal microbiota transplantation (FMT) versus autologous stool as placebo in mild to moderately active adult ulcerative colitis [UC: one type of inflammatory bowel disease (IBD)] patients. This review-commentary examines the current state of knowledge on human gut microbiome (live microbiota + their products and surrounding environment, i.e., fecal matter) and microbial therapeutics from a gastrointestinal (GI) clinician's standpoint. The varied forms of dysbiosis as the target of FMT, recipient donor and placebo considerations are also discussed in respect to randomized control trials in IBD [and the lack thereof in Crohn's disease (CD)] with this unconventional treatment modality.

Designing clinical trials in paediatric inflammatory bowel diseases: a PIBDnet commentary

IntroductionThe optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a...

Spinal Instability in Rats Counteracted by Pentadecapeptide BPC 157

To induce spinal instability, we focused on bilateral facetectomy in rats and possible therapeutic benefit with the stable gastric pentadecapeptide BPC 157 given in the drinking water. Recently, using a well‐designed rat model (L2‐L3 compression), we demonstrated that the stable gastric pentadecapeptide BPC 157 improved the spinal cord injury (FASEB J 2015, 29, 617.5), concluding that under the conditions of one single application, given soon after spinal cord injury, motor function was markedly recovered, axonal and neuronal necrosis was counteracted, as was demyelination and cyst formation. Previously shown to counteract the consequence of peripheral (sciatic) nerve transection/anastomosis, improve nerve healing (Regul Pept. 2010 Feb 25;160(1–3):33–41.), brain trauma (Regul Pept. 2010;160(1–3):26–32.), and various encephalopathies (Curr Pharm Des. 2018;24(18):1990–2001), BPC 157 (LD1 not achieved) was implemented as an anti‐ulcer peptide in inflammatory bowel disease trials and now in a multiple sclerosis trial(Curr Pharm Des. 2018;24(18):1990–2001). In this study, the bilateral paravertebral muscles attached to the L3–L4 segment were peeled from the lumbar spine to expose the posterior bony elements. The rats then underwent complete resection of bilateral L3–L4 facet joints without neural tissue injuries. The medication was given in drinking water (BPC 157 10 ng/kg, 0.16 ng/mL, 12 ml/rat/day) through next 8 weeks, while controls received drinking water only. Radiological assesment of rat spines acquired at 1 week or 8 weeks was conducted (Figure 1). At 1 week, controls and BPC 157 animals exhibited no gross deformity observed in any plane, disk spaces seem unaffected, neural foramen at operated level is slightly widened, though BPC 157 drinking animals had higher bone density overall. At 8 weeks, both groups exhibited no gross deformity observed in any plane, unaffected disk spaces, widened neural foramen at the operated level is slightly widened, though there was an additional discrepancy in bone density overall between groups (BPC 157 having markedly more sclerotic and better defined bones). Also worth noting is the lack of abundant callus formation in the BPC 157 rats whereas the controls have visible callus formation in seemingly random patterns near the affected level. In addition, a significant motor disability which appears in controls immediately upon injury induction, was completely counteracted in BPC 157 drinking rats.Support or Funding InformationThis work was supported by the Ministry of Science, Education and Sports, Republic of Croatia [grant number 108‐1083570‐3635].This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.