(2R,6R)-Hydroxynorketamine for the Treatment of Neuropathic Pain (HNK)

January 5, 2026 updated by: Asokumar Buvanendran, Rush University Medical Center

(2R,6R)-Hydroxynorketamine a Novel Therapeutic Analgesic for the Treatment of Neuropathic Pain: A Randomized Double Blind Cross-Over Trial.

The goal of this randomized double blind three way (1:1:1) cross over clinical trial is to evaluate the effectiveness and duration of analgesia of a single infusion of (2R,6R)-HNK 0.5mg/kg compared with ketamine 0.5mg/kg and saline with a 5-week interval between treatments on pain, pain qualities, physical function, pain interference, sleep disturbance and quality of life in subjects with neuropathic pain of the extremities.

The questions that this study will address are:

  1. What is the analgesic efficacy of (2R,6R)-HNK on pain intensity and pain qualities in patients with chronic (>3 month) neuropathic pain (NP).
  2. What will be the effective duration of a single infusion of (2R,6R)-HNK in patients with NP.
  3. Will (2R,6R)-HNK reduce pain related effects including interference in daily activities of life, sleep disturbances and change the qualities of pain reported by patients.

Participants will receive each of the three study drugs in a random order at 5-week intervals over a 15 week period. The drug will be administered as a 45-minute infusion.

Participants will complete quantitative sensory and pain evaluations and complete patient reported pain outcomes prior to receiving the first study drug and at 7, 14 and 21 and 35 days following study drug administration.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Adult patients (18 to 80 years) with an established diagnosis of chronic (> 3 month) neuropathic pain (NP) of the extremities will be identified and screened for study inclusion. After informed consent is obtained, subject will be randomized into a (2R,6R)-HNK (H), ketamine (K) or saline (S) infusion groups for each of the study drug administration periods. The group sequences for the infusions will be: KSH, HSK, KHS, SKH and HKS and each group will contain 5 subjects at each sequence. Study subjects will be evaluated for at least 7 days prior to the first treatment and for 35 days following each treatment. Researchers involved in the subject's care and assessments will be blinded to group allocation. Safety will be assessed throughout the study. Baseline safety assessments will include height, body mass index (BMI), weight, temperature, medical, visual and ocular history, physical examinations, and vital signs (VS). Prior to study commencement and 28 days after each drug infusion a blood chemistry panel, liver function tests (LFT), a complete blood count (CBC) and a 12-lead electrocardiogram (ECG) will be obtained. A pretreatment quantitative pain evaluation will assess overall pain level, pain tolerance, pinprick hyperalgesia, touch, brush and cold allodynia. Patients will be maintained on their current scheduled analgesic regimen during the study and instructed to use on-demand analgesic only as needed.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients (18 to 75 years) with an established diagnosis of chronic (> 3 month) NP of the extremities.
  • Presence of NP as determined at screening using the 10 item Neuropathic Pain Questionnaire (DN4), with a score of ≥4 required for study inclusion.
  • Ability to read and write English sufficiently to complete study related procedures.
  • A body mass index (BMI) (weight [kg]/height[m ]) between 18 and 35 kg/m (inclusive) and weighs between 50 kg and 120 kg (110 - 264 pounds).
  • Blood pressure with subject is in a supine position for approximately 5 minutes between 90 and 145 mmHg systolic and no higher than 90 mmHg diastolic at baseline.
  • A 12-lead ECG with no clinically significant abnormality as judged by the Investigator and QTc interval ≤ 450 milliseconds at baseline.
  • Resting pulse rate between 45 and 100 beats per minute.
  • Clinical laboratory findings and liver function tests within the normal range, or if outside of the normal ranges, deemed not clinically significant in the opinion of the PI.
  • Agree to provide written informed consent and comply with the rules regarding consumption of alcohol, caffeinated beverages, and tobacco/nicotine products during the study.
  • Patients may be taking scheduled or as needed medications for their chronic neuropathic pain and agree to continue taking the scheduled medications throughout the study period.
  • If the subject experiences pain relief they may elect not to take as needed medications.

Exclusion Criteria:

  • Subjects with suspected increased intracranial or intraocular pressure.
  • Subjects that have previously received ketamine for the treatment of a chronic pain diagnoses.
  • Previous or current participation in any clinical study with an investigational drug, device, or biologic within 30 days.
  • Subjects with severe medical illness including (but not limited to) hepatic, cardiovascular, pulmonary, renal, hematologic, endocrine, gastrointestinal, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease that in the opinion of the PI would endanger the safety of the subject or the validity of the study results.
  • Clinically significant acute illness in the 2 weeks prior to dosing.
  • Inability to effectively communicate with research staff.
  • Subjects with known liver disease.
  • Widespread pain or a diagnosis of fibromyalgia.
  • Current diagnosis of mental illness.
  • Pregnancy.
  • Allergy to ketamine or any study drug.
  • Consumption of beverages or food that contain alcohol, grapefruit, poppy seeds, Brussel sprouts, pomegranate, broccoli, char-grilled meat within 2 days prior to drug administration.
  • Use of tobacco or nicotine-containing products within 4 weeks prior to drug administration.
  • Poor peripheral venous access.
  • Subjects in the opinion of the PI should not participate in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ketamine
Ketamine 0.5mg/kg 45 minute infusion x 1
Drug: Ketamine
Ketamine will be administered over a 45-minute period.
Experimental: (2R,6R)-hydroxynorketamine
(2R,6R)-hydroxynorketamine 0.5mg/kg 45 minute infusion x 1
Drug: (2R,6R)-hydroxynorketamine
(2R,6R)-Hydroxynorketamine hydrochloride will be administered over a 45-minute period.
Placebo Comparator: Saline
Saline 45 minute infusion x 1
Drug: Saline
Saline will be administered over a 45-minute period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain intensity
Time Frame: 35 days
Area under the pain by time curve
35 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain qualities
Time Frame: 35 days
Change in the AUC's of T-metric score for pain qualities from the PROMIS neuropathic pain qualities questionnaire
35 days
PainDETECT questionnaire screening scores
Time Frame: 5 weeks
Assessing weekly change in PainDETECT screening scores. PainDETECT is a patient-reported pain qualities assessment tool developed to screen for neuropathic pain. The assessment scale is scored from -1 to 38. Total scores of 12 or less indicates nociceptive pain, 13-18 represent possible neuropathic pain, and >19 represents >90% likelihood of neuropathic pain.
5 weeks
Analgesic consumption
Time Frame: 5 weeks
Weekly analgesic consumption quantified using the MQS III
5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rush University Medical Center

Collaborators

Congressionally Directed Medical Research Programs

Investigators

  • Principal Investigator: Asokumar Buvanendran, MD, Rush University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 19, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

April 26, 2023

First Submitted That Met QC Criteria

May 8, 2023

First Posted (Actual)

May 18, 2023

Study Record Updates

Last Update Posted (Actual)

January 7, 2026

Last Update Submitted That Met QC Criteria

January 5, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21092004
  • CP220059 (Other Grant/Funding Number: Congressionally Directed Medical Research Programs)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual patient data will be available from the PI, Dr. Asokumar Buvanendran, by request after executing a Data Use Agreement with Rush University. This agreement will indicate the criteria for data access, the conditions for research use, privacy and confidentiality standards to ensure data security at the recipient site, and prohibitions for manipulating data for the purposes of identifying subjects.

IPD Sharing Time Frame

Data will be available approximately 12 months following the closure of the study.

IPD Sharing Access Criteria

Executed Data Use Agreement with Rush University Medical Center

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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