Psilocybin + Psychotherapy for Irritable Bowel Syndrome

Overseen By Erin Mauney, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: TRYP Therapeutics

Must not be taking: Antidepressants, Opioids, Benzodiazepines, others

Disqualifiers: Hypertension, Heart disease, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

14 Participants Needed

Trial Summary

What is the purpose of this trial?

Participants with IBS (all subtypes) and with no exclusionary comorbid psychiatric or medical disorders will be enrolled in the study. This study will involve a randomized waitlist control design to investigate the rapid and sustained effects of TRP-8802 following two experimental sessions in which an oral dose of TRP-8802 is administered to participants with IBS. The study will include clinician and participant ratings of depression and anxiety pre- and post-drug-session, monitor and participant ratings of subjective drug effects during and after each drug session. This study comprises approximately a 28-day screening period (Days 28 to 1). After screening and enrollment, participants will be randomized to an immediate treatment group or a delayed treatment group ("waitlist control" condition). Participants in the immediate treatment group will proceed directly into three weeks of baseline and preparation (Days 1 to 18), a 2-dose administration period (Days 22 and 37), integration (Days 23, 30, 38, and 45), the End of Therapy (EOT) visit (Day 52). Participants in the delayed treatment group will wait 8 weeks after enrollment before beginning the study interventions and neuroimaging assessments. As a safety precaution, participants in the delayed treatment group will be assessed weekly via telephone calls or in-person visits during the wait period (i.e., telephone assessments during post-randomization weeks 1, 2, 3, 4, 5, 6, and 7; in-person assessment during post-randomization week 8) to assess suicide risk to determine if intervention is warranted. During week 8, IBS symptoms will also be assessed. At the end of the delay period, all participants in the delayed treatment group will complete the same intervention as the participants in the immediate treatment group. Validated and commonly used assessment tools will be used to evaluate symptoms at baseline and repeatedly after each session. The weekly average of worst daily pain score and weekly stool frequency and consistency for the 7 days immediately prior to EOT visit will be assessed for change from baseline and at the 3-, 6 , and 12- month follow-up visits (Days 120, 240, 365).

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. Participants must refrain from using antidepressants, psychoactive prescription medications, and certain other drugs. There is a specific requirement to stop taking antidepressants at least 2 weeks (or 4 weeks for fluoxetine) before the screening visit. Additionally, participants must not take any medications with a primary centrally-acting serotonergic effect, and must refrain from using cannabis and other psychoactive drugs during the study. Please consult with the trial team for specific guidance on your medications.

What data supports the idea that Psilocybin + Psychotherapy for Irritable Bowel Syndrome is an effective treatment?

The available research does not provide specific data on the effectiveness of Psilocybin + Psychotherapy for Irritable Bowel Syndrome. Instead, it discusses other treatments like cognitive behavior therapy (CBT) and various medications targeting the brain-gut axis. While these treatments show some promise, there is no direct comparison or data on Psilocybin + Psychotherapy for IBS in the provided information. ^{1 2 3 4 5}

What safety data exists for Psilocybin + Psychotherapy for IBS?

The provided research does not contain specific safety data for Psilocybin + Psychotherapy or TRP-8802 for IBS. The studies focus on other treatments like tegaserod, STW 5, traditional therapies, and Chinese herbal medicine for IBS, none of which mention Psilocybin or TRP-8802. ^{6 7 8 9 10}

Is the drug TRP-8802 a promising treatment for Irritable Bowel Syndrome?

Yes, TRP-8802, which is also known as Psilocybin, is a promising treatment for Irritable Bowel Syndrome because it targets the brain-gut axis, which is crucial in managing IBS symptoms. This drug could help regulate the nervous system and improve communication between the brain and gut, potentially reducing IBS symptoms. ^{1 3 7 11 12}

Research Team

Franklin King, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults aged 21-64 with IBS who've tried at least one diet change and one medication for over six weeks, and have had symptoms for more than a year. They must have a BMI of 18.5-29.9 and their condition can't be explained by another medical issue.

Inclusion Criteria

Your main stomach doctor has thoroughly checked your symptoms and believes that you have irritable bowel syndrome.

You have a body mass index (BMI) between 18.5 and 29.9.

My bowel habits have changed and it's not due to another known medical condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Baseline and Preparation

Participants undergo baseline assessments and preparation for treatment

3 weeks

Multiple visits for assessments and preparation

Treatment

Participants receive two doses of TRP-8802 with integration sessions

4 weeks

2 in-person visits for dosing, 4 integration sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up visits at 3, 6, and 12 months

Treatment Details

Interventions

• TRP-8802

Trial Overview The study tests TRP-8802 combined with psychotherapy on IBS patients. It compares immediate treatment to an 8-week delayed group using clinician/participant ratings of depression/anxiety, subjective drug effects, pain scores, stool frequency/consistency.

Participant Groups

Group I: Waitlist Control Experimental Treatment 2 Interventions

Group II: Open Label Oral Psilocybin Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

TRYP Therapeutics

Lead Sponsor

Trials

4

Recruited

30+

Findings from Research

Irritable bowel syndrome (IBS) affects about 20% of the global population and is characterized by chronic abdominal pain and altered bowel habits, with its pathophysiology linked to dysregulation of the brain-gut axis.

Current treatments for IBS include traditional symptomatic therapies and novel approaches targeting neurotransmitter receptors, such as 5-HT3 antagonists for diarrhea and 5-HT4 agonists for constipation, highlighting the importance of understanding gut-brain communication in developing effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The brain-gut axis in irritable bowel syndrome--clinical aspects. Mach, T.[2022]

Irritable bowel syndrome (IBS) is linked to altered brain-gut interactions, particularly involving serotonin (5-HT) and its receptors, which affect gastrointestinal function and symptom presentation.

The Rome criteria are the standard for diagnosing IBS, focusing on abdominal pain and altered bowel habits, while treatment strategies may include dietary changes, serotonin agonists, and psychological support to improve patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irritable bowel syndrome: update on pathogenesis and management. Alaradi, O., Barkin, JS.[2018]

Emerging pharmaceuticals for treating irritable bowel syndrome (IBS), particularly serotonin receptor modulators, aim to improve therapeutic management by addressing the complex interactions between the enteric and central nervous systems.

The FDA has approved two serotonin receptor modulators specifically for IBS, but the effectiveness of a single therapy remains uncertain due to the multifactorial nature of the disease, which includes biological, psychological, and social influences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update in the pharmaceutical therapy of the irritable bowel syndrome. Thielecke, F., Maxion-Bergemann, S., Abel, F., et al.[2019]

Irritable bowel syndrome (IBS) affects 10-20% of the population, particularly women, and significantly impacts quality of life, necessitating a multifaceted treatment approach that includes dietary, lifestyle, behavioral, and pharmacologic therapies.

Calcium polycarbophil has been identified as a beneficial treatment for IBS patients experiencing constipation or alternating diarrhea and constipation, highlighting the importance of tailored therapies based on individual symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of irritable bowel syndrome. Torii, A., Toda, G.[2019]

The IBS Outcome Study (IBSOS) is a multicenter trial involving 171 patients that aims to evaluate the efficacy of a self-administered version of cognitive behavior therapy (CBT) for treating irritable bowel syndrome (IBS), comparing it to standard CBT and an attention control.

This study seeks to determine not only the effectiveness of self-administered CBT in reducing IBS symptoms and improving quality of life but also to explore the durability of treatment effects over 12 months and identify patient characteristics that may influence outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Irritable Bowel Syndrome Outcome Study (IBSOS): rationale and design of a randomized, placebo-controlled trial with 12 month follow up of self- versus clinician-administered CBT for moderate to severe irritable bowel syndrome. Lackner, JM., Keefer, L., Jaccard, J., et al.[2022]

In an 8-week study involving 850 patients with non-diarrhoea irritable bowel syndrome (non-D-IBS), tegaserod was found to be safe and well-tolerated, with 66% of patients reporting relief from symptoms after treatment.

While 38% of patients experienced adverse events, primarily mild to moderate diarrhea, these were mostly transient and resolved with continued treatment, indicating that tegaserod can be an effective option for managing non-D-IBS symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tegaserod is safe, well tolerated and effective in the treatment of patients with non-diarrhoea irritable bowel syndrome. Fried, M., Beglinger, C., Bobalj, NG., et al.[2019]

Irritable bowel syndrome (IBS) affects about 11% of the global population and is characterized by various symptoms due to complex interactions between the gut and brain, necessitating multi-targeted treatment approaches.

STW 5, a herbal preparation with nine extracts, has shown efficacy in addressing multiple IBS-related mechanisms, including gastrointestinal motility, inflammation, and gut microbiota, making it a promising multi-targeted treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-target Treatment for Irritable Bowel Syndrome with STW 5: Pharmacological Modes of Action. Allescher, HD., Burgell, R., Malfertheiner, P., et al.[2021]

Current therapies for Irritable Bowel Syndrome (IBS), including traditional treatments like antidepressants and fiber supplements, as well as alternative therapies like peppermint oil and herbal supplements, lack sufficient evidence to support their effectiveness.

The review highlights that no IBS treatments can be reliably recommended due to inadequate high-quality studies demonstrating their efficacy, emphasizing the need for better-designed clinical trials in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traditional therapies for irritable bowel syndrome: an evidence-based appraisal. Fennerty, MB.[2005]

Chinese herbal medicine (CHM) significantly improves global IBS symptoms compared to placebo, with a relative risk of 1.76 based on a meta-analysis of 10 trials involving 2,501 participants.

While CHM is effective for relieving IBS symptoms, it is associated with a higher rate of adverse events compared to placebo, indicating a need for careful consideration of its safety in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chinese Herbal Medicine for Irritable Bowel Syndrome: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials. Zheng, H., Jin, S., Shen, YL., et al.[2021]

In clinical trials for irritable bowel syndrome (IBS), a higher incidence of adverse events (AEs) in patients receiving active treatment is linked to better reported outcomes, suggesting that AEs may influence patient perceptions of treatment efficacy.

The study found a significant correlation between the attributable drug benefit and the average risk difference of AEs between treatment and placebo groups, indicating that AEs could lead to unblinding and affect the perceived effectiveness of therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events appear to unblind clinical trials in irritable bowel syndrome. Shah, E., Triantafyllou, K., Hana, AA., et al.[2014]

Cognitive-behavioral therapy (CBT) has been shown to significantly reduce the severity of irritable bowel syndrome (IBS) symptoms and improve quality of life, based on multiple randomized controlled trials.

Despite its proven efficacy, access to CBT for IBS is limited due to a shortage of trained therapists, highlighting the need for increased training and the development of telemedicine platforms to make this treatment more widely available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive-behavioral therapy for patients with irritable bowel syndrome: current insights. Kinsinger, SW.[2022]

In a pilot study of irritable bowel syndrome (IBS) patients, distinct changes in endocannabinoid levels were observed: IBS-D patients had higher 2-AG and lower OEA and PEA levels, while IBS-C patients had higher OEA levels, indicating a potential link between these changes and IBS symptoms.

The study suggests that the endocannabinoid system (ECS) plays a role in IBS, as lower levels of PEA were associated with cramping abdominal pain, and reduced FAAH expression was noted in IBS-C patients, highlighting the ECS's involvement in the disorder's pathophysiology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocannabinoid and cannabinoid-like fatty acid amide levels correlate with pain-related symptoms in patients with IBS-D and IBS-C: a pilot study. Fichna, J., Wood, JT., Papanastasiou, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

The brain-gut axis in irritable bowel syndrome--clinical aspects. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Irritable bowel syndrome: update on pathogenesis and management. [2018]

3. India pubmed.ncbi.nlm.nih.gov

Update in the pharmaceutical therapy of the irritable bowel syndrome. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

Management of irritable bowel syndrome. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

The Irritable Bowel Syndrome Outcome Study (IBSOS): rationale and design of a randomized, placebo-controlled trial with 12 month follow up of self- versus clinician-administered CBT for moderate to severe irritable bowel syndrome. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Tegaserod is safe, well tolerated and effective in the treatment of patients with non-diarrhoea irritable bowel syndrome. [2019]

7. Romania pubmed.ncbi.nlm.nih.gov

Multi-target Treatment for Irritable Bowel Syndrome with STW 5: Pharmacological Modes of Action. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Traditional therapies for irritable bowel syndrome: an evidence-based appraisal. [2005]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Chinese Herbal Medicine for Irritable Bowel Syndrome: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Adverse events appear to unblind clinical trials in irritable bowel syndrome. [2014]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Cognitive-behavioral therapy for patients with irritable bowel syndrome: current insights. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Endocannabinoid and cannabinoid-like fatty acid amide levels correlate with pain-related symptoms in patients with IBS-D and IBS-C: a pilot study. [2022]