Outpatient ketamine treatment for phantom limb pain (six-month protocol)

Phantom Limb Pain Ketamine Treatment Study

This study will try outpatient intramuscular ketamine to see if it reduces phantom limb pain in adults who currently have PLP.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: The Ketamine Research Foundation (Academic / other)
• Locations: 4 sites (Sacramento, California and 3 other locations)
• Trial ID: NCT07276542 on ClinicalTrials.gov

What this trial studies

This interventional Phase 2/3 protocol will enroll 25–30 adults with ongoing phantom limb pain to receive intramuscular ketamine with a dose-finding phase followed by continuation dosing over six months and a required minimum remission period of seven days between treatment sessions. Treatments are delivered in outpatient clinic settings at multiple regional sites and include safety monitoring and at least one year of follow-up. The protocol is FDA- and IRB-approved and excludes patients with uncontrolled hypertension or positive pregnancy tests, and requires temporary avoidance of alcohol, marijuana, nicotine, and other intoxicants around dosing. The study aims to capture pain frequency, intensity, duration of remission, and adverse events to clarify ketamine’s utility for PLP.

Who should consider this trial

Good fit: Adults with ongoing phantom limb pain who can attend outpatient visits and live within about 50 miles of the Bay Area, Los Angeles, Albuquerque, or Sacramento study sites are ideal candidates.

Not a fit: Patients with uncontrolled high blood pressure, pregnant people, or those unable to abstain from intoxicants around dosing or to commit to the follow-up schedule may not benefit or be ineligible.

Why it matters

Potential benefit: If successful, ketamine could reduce the frequency and severity of phantom limb pain and produce longer pain-free intervals for affected patients.

How similar studies have performed: Ketamine has shown benefit in various chronic pain and neurological conditions and there are case reports suggesting long remissions in phantom limb pain, but high-quality randomized evidence for PLP remains limited.

Eligibility criteria

Inclusion Criteria:

* Presence of phantom limb pain at the time of administration of ketamine.
* Willingness to participate in the study and follow-up over a year long period. Living Within a 50 mile radius of our study sites: Bay Area, Los Angeles, Albuquerque, Sacramento, Los Angeles
* Provision of signed and dated, written informed consent prior to any study-specific procedures.
* If female, must have a negative pregnancy test at Screening and any subsequent administration of ketamine. Sexually active females and male partners must be using adequate birth control measures during the duration of the study when ketamine will be administered and for one week after the last administration of ketamine.
* Patient agrees to withhold alcohol, marijuana, nicotine products, and any other intoxicants for at least 24 hours
* Normotensive-defined as Abnormal VS, after 5 minutes supine rest at Screening or on Day -1, defined as any of the following:

Systolic BP\> 150 mmHg.

* Diastolic BP\> 105 mmHg.
* HR \<50 or \>110 bpm.

  * Not on Medications that would blunt ketamine's effects
  * 18-65
  * No prior history of treatment with ketamine for PLP.

Exclusion Criteria:

Exclusion Criteria

* History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study.
* Vulnerable persons are Excluded from the study. This includes subjects with known psychotic illness, mania, significant neurologic disorders, elevated intraocular and or intracranial pressures
* Exclusion of subjects with abnormal baseline hepatic and renal lab tests.
* Exclusion of subjects with cardiovascular disease, arrythmias, or abnormal EKGs.
* The presence of any medication that might cause an adverse reaction with ketamine.
* The Ketalar Label as cited by FDA includes Drug Interactions particular to anesthesia and the use of IV boluses at far higher dosages than those used in our study. In Review of these:

Theophylline Or Aminophyline --Excluded

* Sympathomimetics And Vasopressin-Excluded
* Benzodiazepines-PLP patients may be on benzodiazepines or other anxiolytic medications, Subjects will be asked to suspend daytime use of these whenever possible recognizing that anxiety is an often present symptom within the PLP complex. Recognition of a possible increase in sedation due to the concomitant presence of a benzodiazepine with ketamine may lead to a lowering of the ketamine dosage. Nighttime use of a benzodiazepine for treatment of insomnia will not be discontinued unless the dosage is high and considered to have a sedating effect on the degree of ketamine's sedation the next day. The length of time between nighttime use and administration of ketamine during the day should diminish the effects of the nighttime medication.
* Opioid Analgesics -PLP subjects most likely will have been or will be receiving opiates for pain relief, Concomitant use of ketamine and opiates in outpatient settings for analgesia is a common and accepted practice. Withdrawing opiates for ketamine administered in subanesthetic doses is not appropriate. In several studies ketamine has been shown to reduce the amount of opioids needed for analgesia, It is the hope of this study that successful treatment with ketamine will enable reduction or cessation of opioid use, In our vast clinical experience, we have treated with ketamine at subanesthetic doses patients on opiates without adverse effects.
* Subjects on long-acting opioids such as methadone or extended-release opioids are excluded.
* Subjects with opioid use 50 mg/day MME (morphine milliequivalents) within 1 week of initial ketamine administration are excluded.
* Subjects with +UDS (urine drug screen) for ketamine, cocaine, methamphetamine, PCP, or other substances of abuse are excluded.
* Subjects who have used THC may be enrolled but must have abstained from THC for at least 3 days prior to each ketamine session

Concomitant medications:

* Oral IR (immediate release) opioid mu agonists up to 50 mg/day MME (morphine milliequivalents) are allowed (e.g., hydromorphone, oxycodone, morphine, and hydrocodone).
* No increases of any opioids or other concomitant medications, or addition of new medications or therapies for PLP will be allowed during the study.
* All concomitant medications, including type and amount, will be recorded by study participants in their daily diaries and reviewed by study staff before each treatment session and any scheduled telephone calls.
* Participants will not receive opioids 4 hours before or after ketamine administration.
* Laboratory assessments: Subjects with abnormal baseline hepatic or renal lab tests are to be excluded. In addition, obtain the following laboratory tests at the following times: CBC, hepatic and renal labs at 3 months and 6 months. Follow-up abnormal laboratory values.
* Or Other CNS Depressants-gabapentin may well be prescribed for patients with PLP as is true for pregabalin, Whenever possible subjects will be asked to withhold these for at least 4 hours prior and not resume for at least 4 hours after the last administration of ketamine. This is consistent with two half-lives of ketamine
* Alcohol-Daily use exceeding 2 US Standard drinks. No alcohol use in 24 hours preceding a ketamine session.
* Stimulants-Subjects will be asked to withhold stimulants for 5-12 hours prior to administration of ketamine depending on the duration of action of the particular preparation and not resume until the next day after treatment.

Inclusion Criteria:

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Where this trial is running

Sacramento, California and 3 other locations

• Shamynds — Sacramento, California, United States (Recruiting)
• Ketamine Research Foundation — San Anselmo, California, United States (Recruiting)
• Mystic Health — Santa Monica, California, United States (Recruiting)
• Lisa Feierman MD — Albuquerque, New Mexico, United States (Recruiting)

Study contacts

• Study coordinator: Philip E Wolfson, MD

Conditions Phantom Limb Syndrome With Pain; Phantom Limb Pain, PLP. ketamine, ketamine and pain, ketamine assisted psychotherapy