Assessment of Psilocybin (TRP-8802) in Concert With Psychotherapy in Patients With Irritable Bowel Syndrome (IBS)

NCT06206265 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: TRYP-003
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Irritable Bowel Syndrome

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events - Hypertension

  Incidence of dosing episodes resulting in patient's blood pressure \>200 systolic or \>110 diastolic for more than 15 minutes (i.e. 4 consecutive readings)

  Immediately after the intervention

• Incidence of Treatment-Emergent Adverse Events - Abuse-Related Psychological Events

  Presence of "severe" or "extremely severe" (as measured by the Brief Psychiatric Rating Scale \[BPRS\] hallucinations, psychosis, changes in mood, impaired cognition, attention, psychomotor effects, or inappropriate affect. Note: minimum-maximum scale on BPRS = 0-7, higher score = more severe outcome.

  Immediately after the intervention

• Incidence of Treatment-Emergent Adverse Events - EKG QT Prolongation

  Incidence of prolonged QTc (\>460ms for women and \>450 for men) after receiving at least one dose of psilocybin

  Through study completion, an average of 4 months

Secondary Outcomes (7)

• Stool consistency

  Through study completion, an average of 4 months

• Stool frequency

  Through study completion, an average of 4 months

• Abdominal pain

  Through study completion, an average of 4 months

• Anxiety and depression

  Through study completion, an average of 4 months

• Severity of IBS

  Through study completion, an average of 4 months

Other Outcomes (7)

• Functional magnetic resonance imaging (fMRI) functional connectivity

  Through study completion, an average of 4 months

• Heart rate variability (HRV)

  Through study completion, an average of 4 months

• Inflammatory biomarkers: High sensitivity C-reactive protein (hsCRP)

  Through study completion, an average of 4 months

Study Arms (2)

Open Label Oral Psilocybin

EXPERIMENTAL

Drug: TRYP-0082; Behavioral: Psychotherapy

Waitlist Control

OTHER

Drug: TRYP-0082; Behavioral: Psychotherapy

Interventions

TRYP-0082 DRUG

Participants will receive one dose of 25 mg of oral psilocybin on the first dosing day and a second dose of 25mg oral psilocybin on the second dosing day. TRP 8802 will be administered in a comfortable setting under the guidance of the same two therapists from the preparation period. Participants will have an in-person study visit following the resolution of the psychoactive effects of the psilocybin (as determined by the therapists in discussion with the participant) to ensure participant's safety and comfort.

Open Label Oral Psilocybin; Waitlist Control

Psychotherapy BEHAVIORAL

Participants will receive one dose of 25 mg of oral psilocybin on the first dosing day and a second dose of 25mg oral psilocybin on the second dosing day. TRP 8802 will be administered in a comfortable setting under the guidance of the same two therapists from the preparation period. Participants will have an in-person study visit following the resolution of the psychoactive effects of the psilocybin (as determined by the therapists in discussion with the participant) to ensure participant's safety and comfort.

Open Label Oral Psilocybin; Waitlist Control

Eligibility Criteria

• Age: 21 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age
• \. Participant must be 21 to 64 years of age, inclusive, at the time of signing the informed consent form.
• Type of Participant and Disease Characteristics
• Participant has a body mass index (BMI) between 18.5 and 29.9
• Have a clinical diagnosis of IBS (any subtype) as defined by the Rome IV clinical criteria:
• Abdominal pain at least 4 days per month over at least 2 months associated with one or more of the following:
• i. Related to defecation ii. A change in frequency of stool iii. A change in form (appearance) of stool iv. After appropriate evaluation, the symptoms cannot be fully explained by another medical condition
• Have "treatment resistant" IBS (Rajagopalan 1997) by having all of the following:
• symptoms for more than 12 months by history
• received adequate explanation and reassurance for symptoms as documented by a gastroenterologist in the medical record. This means the patient's primary gastroenterologist will document that they have conducted an evaluation that is within appropriate standards of practice to exclude other medical conditions, and that in their opinion irritable bowel syndrome is the most appropriate diagnosis. The patient's primary gastroenterologist will also document that they have discussed this evaluation and diagnosis with the patient.
• tried at least one dietary intervention by history
• tried at least one pharmacologic agent for at least six weeks by history
• Have attempted a gut-brain behavior therapy for at least six weeks by history
• Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least 2 months prior to screening and is expected to remain stable during participation in the study.
• Participant must not use tobacco or other nicotine containing products (e.g., vape pens) by history.

You may not qualify if:

• Medical Conditions
• Participant has the following vital sign measurements (taken after 5 minutes of sitting down) during screening visit: SBP\>139 mmHg, DBP \> 89 mmHg, and/or HR \> 90bpm
• Participant has a history of valvular heart disease reported during screening
• Participant has a history of pulmonary hypertension reported during screening
• Participant has moderate to severe hepatic impairment (Child Pugh Class B and C) as determined by presence of ascites or encephalopathy and scoring of albumin, bilirubin, and INR on screening labs
• Participant has one of the following gastrointestinal medical conditions: inflammatory bowel disease (ulcerative colitis or Crohn's disease), celiac disease, chronic idiopathic constipation, or eosinophilic esophagitis reported during screening
• Participant has had (within the past 1 year) a cardiovascular condition such as coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation), prolonged QTc interval (i.e., QTc \> 450 msec), artificial heart valve, or transient ischemic attack reported during screening
• Participant has epilepsy with a history of seizures reported during screening
• Participant has insulin-dependent diabetes reported during screening
• Participant is taking an oral hypoglycemic agent and has a history of hypoglycemia.
• Participant has active auto-immune disease (e.g., lupus, rheumatoid arthritis) reported during screening
• Participant has a current or past history of meeting Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or bipolar I or II disorder measured via SCID-5 and SCID-5-PD.
• Participant has a current or past history (within 1 year) of meeting DSM-5 criteria for a moderate or severe alcohol, tobacco, or other drug use disorder (excluding caffeine) measured via relevant questions from the SCID-5 during screening
• Participant has a history of a medically significant suicide attempt, meaning a suicide attempt leading to an emergency room visit or inpatient hospitalization for any length of time.
• Participant does not meet institutional guidelines and safety measures for MRI (e.g., has metal in the body or severe claustrophobia) Prior/Concomitant Therapy

Sponsors & Collaborators

• TRYP Therapeutics: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Psychotherapy

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities

Study Officials

• Franklin King, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be randomized either into the immediate therapy vs. waitlist control. Patients in the waitlist control will eventually be offered the same therapy at 8 weeks post enrollment. The delayed treatment arm will initiate therapy on the same schedule as the immediate treatment arm.

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: January 16, 2024
• Study Start: January 17, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)