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Pain, NeuropathicPhase 1/2HNKNCT05864053

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

A Phase 1/2 study testing Ketamine, (2R,6R)-hydroxynorketamine and Saline in people with Pain, Neuropathic, run by Rush University Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pain, Neuropathic
What is being tested?
Ketamine, (2R,6R)-hydroxynorketamine and Saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
25 participants
Where
1 siteUnited States
Study dates
19 Sep 2024to Aug 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Robert J McCarthy, Pharm D contact

3125630448

robert_j_mccarthy@rush.edu

Rachel Granito, BS contact

3125632028

rachel_granito@rush.edu

United States1 site, 1 recruiting

  • Rush University Medical Center

    Chicago, Illinois, 60612

    Robert J McCarthy, Pharm D, 3125630448, robert_j_mccarthy@rush.edu

    Daniel Torrez, BS, 3129422741, daniel_torrez@rush.edu

    Recruiting

Other trials in United States

About this study

Official title: (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:

Read more
  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.

Read the 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.

Being tested
Ketamine, (2R,6R)-hydroxynorketamine, Saline
Keywords
pain, pain, chronic, pain, neuropathic, non-opioid analgesic, ketamine, (2R,6R)-hydroxynorketamine
Medical subject headings
Neuralgia, Pain, Chronic Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KetamineDrug

    Ketamine will be administered over a 45-minute period.

  • (2R,6R)-hydroxynorketamineDrug

    (2R,6R)-Hydroxynorketamine hydrochloride will be administered over a 45-minute period.

  • SalineDrug

    Saline will be administered over a 45-minute period.

Study groups in NCT05864053
Study groupRoleWhat they receive
KetamineActive comparatorKetamine 0.5mg/kg 45 minute infusion x 1
Receives: Drug: Ketamine
(2R,6R)-hydroxynorketamineExperimental(2R,6R)-hydroxynorketamine 0.5mg/kg 45 minute infusion x 1
Receives: Drug: (2R,6R)-hydroxynorketamine
SalinePlacebo comparatorSaline 45 minute infusion x 1
Receives: Drug: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pain intensity

    Area under the pain by time curve

    Measured: 35 days

Secondary outcomes (3)

  1. Pain qualities

    Change in the AUC's of T-metric score for pain qualities from the PROMIS neuropathic pain qualities questionnaire

    Measured: 35 days

  2. PainDETECT questionnaire screening scores

    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.

    Measured: 5 weeks

  3. Analgesic consumption

    Weekly analgesic consumption quantified using the MQS III

    Measured: 5 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2023
  2. Study start19 Sep 2024
  3. Primary completionApr 2027 (estimated)
  4. Study completionAug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Randomized double blind three way (1:1:1) cross over clinical trial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05864053
Sponsor's protocol ID
21092004
Other IDs
CP220059
Acronym
HNK
Status last verified
Jul 2026
First submitted
26 Apr 2023
Last updated
3 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Yawn BP, Wollan PC, Weingarten TN, Watson JC, Hooten WM, Melton LJ 3rd. The prevalence of neuropathic pain: clinical evaluation compared with screening tools in a community population. Pain Med. 2009 Apr;10(3):586-93. doi: 10.1111/j.1526-4637.2009.00588.x. Epub 2009 Mar 17.

    PubMed 20849570

  • McCarberg BH, Billington R. Consequences of neuropathic pain: quality-of-life issues and associated costs. Am J Manag Care. 2006 Jun;12(9 Suppl):S263-8.

    PubMed 16774458

  • Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015 Feb;14(2):162-73. doi: 10.1016/S1474-4422(14)70251-0. Epub 2015 Jan 7.

    PubMed 25575710

  • Attal N. Pharmacological treatments of neuropathic pain: The latest recommendations. Rev Neurol (Paris). 2019 Jan-Feb;175(1-2):46-50. doi: 10.1016/j.neurol.2018.08.005. Epub 2018 Oct 11.

    PubMed 30318260

  • Cohen SP, Bhatia A, Buvanendran A, Schwenk ES, Wasan AD, Hurley RW, Viscusi ER, Narouze S, Davis FN, Ritchie EC, Lubenow TR, Hooten WM. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):521-546. doi: 10.1097/AAP.0000000000000808.

    PubMed 29870458

  • Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466. doi: 10.1097/AAP.0000000000000806.

    PubMed 29870457

  • Jouguelet-Lacoste J, La Colla L, Schilling D, Chelly JE. The use of intravenous infusion or single dose of low-dose ketamine for postoperative analgesia: a review of the current literature. Pain Med. 2015 Feb;16(2):383-403. doi: 10.1111/pme.12619. Epub 2014 Dec 19.

    PubMed 25530168

  • Sleigh J, Harvey M, Voss L, Denny B. Ketamine - More mechanisms of action than just NMDA blockade. Trends in Anaesthesia and Critical Care 2014; 4:76-81.

  • Humo M, Ayazgok B, Becker LJ, Waltisperger E, Rantamaki T, Yalcin I. Ketamine induces rapid and sustained antidepressant-like effects in chronic pain induced depression: Role of MAPK signaling pathway. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jun 8;100:109898. doi: 10.1016/j.pnpbp.2020.109898. Epub 2020 Feb 25.

    PubMed 32109506

  • Tran K, McCormack S. Ketamine for Chronic Non-Cancer Pain: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2020 May 28. Available from http://www.ncbi.nlm.nih.gov/books/NBK564230/

    PubMed 33231962

  • Chitneni A, Patil A, Dalal S, Ghorayeb JH, Pham YN, Grigoropoulos G. Use of Ketamine Infusions for Treatment of Complex Regional Pain Syndrome: A Systematic Review. Cureus. 2021 Oct 19;13(10):e18910. doi: 10.7759/cureus.18910. eCollection 2021 Oct.

    PubMed 34820225

  • Velzen MV, Dahan JDC, van Dorp ELA, Mogil JS, Hooijmans CR, Dahan A. Efficacy of ketamine in relieving neuropathic pain: a systematic review and meta-analysis of animal studies. Pain. 2021 Sep 1;162(9):2320-2330. doi: 10.1097/j.pain.0000000000002231.

    PubMed 33790195

  • Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP. Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesth Analg. 2019 Jul;129(1):241-254. doi: 10.1213/ANE.0000000000004185.

    PubMed 31082965

  • Amr YM. Multi-day low dose ketamine infusion as adjuvant to oral gabapentin in spinal cord injury related chronic pain: a prospective, randomized, double blind trial. Pain Physician. 2010 May-Jun;13(3):245-9.

    PubMed 20495588

  • Pickering G, Pereira B, Morel V, Corriger A, Giron F, Marcaillou F, Bidar-Beauvallot A, Chandeze E, Lambert C, Bernard L, Delage N. Ketamine and Magnesium for Refractory Neuropathic Pain: A Randomized, Double-blind, Crossover Trial. Anesthesiology. 2020 Jul;133(1):154-164. doi: 10.1097/ALN.0000000000003345.

    PubMed 32384291

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ketamine, (2R,6R)-hydroxynorketamine and Saline in people with Pain, Neuropathic, run by Rush University Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Robert J McCarthy, Pharm D (3125630448, robert_j_mccarthy@rush.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pain intensity (time frame: 35 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05864053, which also lists 52 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026.

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