Psychotherapy for Ketamine's Enhanced Durability in Chronic Neuropathic Pain: A Randomized Controlled Pilot Trial (PSYKED-NP)

The purpose of the study is to investigate new therapies to alleviate pain on neuropathic chronic pain. At this time, the main purpose is to complete a feasibility or pilot study with 30 participants suffering from neuropathic chronic pain. Participants will be randomized to (1) Ketamine (Hydrochloride) HCL; (2) psychotherapy (using Cognitive Behavioral Therapy); or (3) a combination of Ketamine HL and psychotherapy.

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: Ketamine Hydrochloride; Behavioral: Cognitive Behavioral Therapy; Other: Ketamine + Cognitive Behavioral Therapy

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥18 years of age
2. Diagnosis of chronic neuropathic pain as determined by a pain specialist with moderate-to-severe neuropathic pain as per ID pain questionnaire, with mean pain scores > 3 on a numeric rating scale (NRS), in the 7 days preceding inclusion
3. For participants of childbearing potential, use highly effective or double-barrier methods of contraception. Abstinence is acceptable if it is the preferred and usual lifestyle of the participant
4. Capacity to provide informed consent

Exclusion Criteria:

1. Patients less than 18 years of age
2. Current or lifetime history of schizophrenia, psychotic disorder, bipolar disorder, or borderline personality disorder
3. Known history of hypersensitivity or allergy to Ketamine-HCL
4. Current history of dissociative disorders
5. Current concomitant use of theophylline or aminophylline
6. Current elevated intracranial pressure
7. Pregnancy or ongoing breastfeeding in female participants
8. Concomitant active substance use in the 6 months preceding enrolment (amphetamines, alcohol, and ketamine)
9. Contraindication to receiving Ketamine-HCL (e.g. current or lifetime history of cerebrovascular accident; current significant hypertension [systolic blood pressure higher than 160 mmHg and/or diastolic blood pressure higher than 100 mmHg]; current severe cardiac decompensation [e.g. presence of dyspnea, peripheral edema, elevated jugular venous pressure, hepatomegaly, pulmonary rales, pleural effusions])

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketamine only	Drug: Ketamine Hydrochloride; Ketamine-HCL IV 1mg/kg (up to 100 mg) over 2 hours, on weeks 2, 7, and 12.
Active Comparator: Psychotherapy only	Behavioral: Cognitive Behavioral Therapy; Cognitive Behavioural Therapy/ Mindfulness Based Meditation therapy (CBT/MM) remotely for 16 hours between weeks 1 to 16 inclusive + in-person sessions on weeks 2, 7 and 12
Experimental: Ketamine + Psychotherapy	Other: Ketamine + Cognitive Behavioral Therapy; Ketamine-HCL + CBT/MM according to the same directions specified in Arm 1 and Arm 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events	Safety and tolerability	2 years
Recruitment rate	Recruitment rate and withdrawal rate (Acceptability and feasibility study)	2 years
Adherence rate	Feasibility	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Reported Outcomes Measurement Information System Pain Interference, PROMIS 6 a. Pain Interference,	PROMIS-PI -Short form 6 a. - pain interference scale- 6 items, 5 likert scale The higher the score the higher the interference from pain)	20 weeks
Patient-Reported Outcomes Measurement Information System Pain Interference (PROMIS) Pain Intensity, 1 a.	PROMIS-PI - 1 a. pain intensity scale- 0 to 10 (The higher the number the higher the pain intensity)	20 weeks

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Unity Health Toronto

Publications and helpful links

General Publications

• Goel A, Kapoor B, Chan H, Ladha K, Katz J, Clarke H, Pazmino-Canizares J, Thomas Z, Philip K, Mattina G, Ritvo P. Psychotherapy for Ketamine's Enhanced Durability in Chronic Neuropathic Pain: Protocol for a Pilot Randomized Controlled Trial. JMIR Res Protoc. 2024 Apr 17;13:e54406. doi: 10.2196/54406.

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Actual): July 24, 2025
• Study Completion (Actual): July 24, 2025

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: November 28, 2022
• First Posted (Actual): December 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Ketamine; Feasibility trial; Cognitive behavioural therapy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neuralgia; Organic Chemicals; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Ketamine; Cognitive Behavioral Therapy
• Other Study ID Numbers: P-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data has been planned to be shared with other researchers at this point, since this is a feasibility study with only 30 participants

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No