NeuroGuard: Psilocybin Trial for Preventing Chemo-induced Neuropathy

Not Applicable

Not yet recruiting

• Conditions: Psilocybin; Neuropathy
• Interventions: Drug: Psilocybin (drug); Other: Standard of Care (SOC)

• Registration Number: NCT07227909
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

To learn if psilocybin can help to prevent or decrease the severity of chemotherapy-induced peripheral neuropathy (CIPN) in patients who are receiving chemotherapy for the treatment of breast, colorectal, and In this study, psilocybin is being compared to standard supportive care and to a placebo.

Detailed Description

Primary Objective

1\. To assess the efficacy of psilocybin in the prevention or mitigation of chemotherapy-induced peripheral neuropathy (CIPN) in individuals undergoing adjuvant neurotoxic chemotherapy (i.e., taxanes, platinum-based compounds) for breast, colorectal, and head \& neck cancers. The primary endpoint is the proportion of participants with a ≥25% increase (worsening) from baseline to Week 12 on the EORTC QLQ-CIPN20 sensory subscale.

The primary comparison is 25 mg psilocybin vs pooled control (standard of care + 1 mg subperceptual psilocybin), tested two-sided at α=0.05. If significant, two confirmatory pairwise tests (25 mg vs SOC; 25 mg vs 1 mg) will be performed with Hochberg multiplicity control.

Hypothesis: Prophylactic psilocybin administered in four doses (two pre-chemotherapy and two during chemotherapy) will reduce the severity of CIPN as measured by the proportion of participants reporting a 25% or greater increase in CIPN on the EORTC QLQ-CIPN20 sensory subscale compared to placebo or SOC.

Secondary Objectives

1. Determine whether prophylactic psilocybin reduces rates of dose-liming modifications to chemotherapy as result of peripheral neurotoxicity. Dose modifications are defined by either a change in frequency or reduced chemotherapy dose during the 12-week study period. Dose modification decisions will be made by the participant's independent, primary clinician.

2. Determine whether prophylactic psilocybin decreases incidence and severity of CIPN as measured by the NCI-CTCAE criteria

3. Determine whether psilocybin-assisted psychotherapy improves measures of quality of life (e.g., sleep, pain, fatigue, functional status) and psychosocial well-being (e.g., mental health, finding meaning, and post-traumatic growth), as measured by the following: PROMIS-10, PROMIS-A, PROMIS-D, FACT-Cog, PSQI, BFI, MDASI, MEQ30 (mystical experience), Flourishing scale.

4. Determine whether psilocybin-assisted psychotherapy improves functional status per clinicianrated outcome measures.

5. Assess the effects of psilocybin-assisted psychotherapy on all-cause cancer treatment adherence determined by the likelihood that participants will follow the prescribed treatment (adherence) and continue the treatment for the duration prescribed (persistence) for these maintenance therapies.

Study Timeline

• Status Verified: 2025-11
• Study First Submitted: 2025-11-12
• Study First Submitted QC: 2025-11-12
• Last Update Submitted: 2025-11-12
• Study First Posted: 2025-11-13
• Last Update Posted: 2025-11-13
• Study Start: 2026-05-04
• Primary Completion: 2029-01-31
• Study Completion: 2031-01-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 83

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Psilocybin (drug)	Two supervised oral doses 1 week apart prior to chemotherapy cycle 1 (Day 7 and Day 14), followed by two monthly supervised doses prior to chemotherapy cycles 2 and 3 (Day 42 and Day 70); total 4 doses.
Arm B	Psilocybin (drug)	Subperceptual dosing every other day for 2 weeks during the pre-chemotherapy run-in (mailed 7×1 mg capsules in tamperevident packaging) prior to the first three cycles as above (21 total doses)
Arm C	Standard of Care (SOC)	Standard of Care: Chemotherapy and supportive care per institutional guidelines; no study drug.

Primary Outcome Measures

Name	Time	Method
Safety and adverse events (AEs)	Through study completion; an average of 1 year	Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

Trial Locations

Locations (1)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States