Ketamine for Refractory Chronic Migraine: a Pilot Study

• ClinicalTrials.gov Identifier: NCT03896256
• Recruitment Status: Completed
• First Posted: March 29, 2019
• Last Update Posted: March 11, 2020
• Sponsor: Thomas Jefferson University
• Information provided by (Responsible Party): Eric Schwenk, Thomas Jefferson University

Study Description

Brief Summary:

Ketamine is a drug used for anesthesia but at low doses it is a very effective pain reliever in several chronic conditions. Preliminary studies have shown that ketamine might be effective for patients with refractory chronic migraine, which is a severe type of headache for which patients usually have tried and failed many medications and can cause severe disability to their lives. This study will evaluate ketamine prospectively when given to patients who have "failed" an initial inpatient treatment.

Condition or disease	Intervention/treatment	Phase
Migraine Headache With Intractable Migraine	Drug: ketamine infusion	Early Phase 1

Detailed Description:

This study is a comparison between ketamine, used in the standard fashion at Thomas Jefferson University Hospital (TJUH) for 5 days, and past data collected from inpatient treatment at Methodist Hospital. The collection of blood samples is the only experimental part of the study.

Eligible patients will be identified by a study team member at the end of inpatient treatment at Methodist Hospital. The study will be explained to patients at that time. Patients who express interest in participation will be given a consent packet to take home and bring to their office visit at Jefferson Headache Center prior to admission to TJUH for ketamine infusions. Patients will be given the time to read over the study information and have all questions answered to their satisfaction. The will provide informed consent at the end of the office visit if they choose to participate. Baseline demographic information and past medical history including current medications and medications previously tried will be collected. Patients and assessors will not be blinded to treatment.

When the patient is admitted to the hospital for treatment, the neurology team will be the admitting team and will consult the Acute Pain Service (APS) for assistance with management of ketamine, which is standard practice when ketamine is used for headache treatment at TJUH. Patients will be admitted for a total of 5 full days from the time of admission until discharge. Adjustments to ketamine infusion will be made according to standard APS protocol and data will be collected by the research coordinator or other study team personnel. A standard 11-point numeric rating scale (NRS) will be used to obtain pain ratings and they will be collected twice daily. A 4-point pain assessment scale (0=none, 1=mild, 2=moderate, 3=severe) will also be used. Blood samples will be collected at baseline and at 24 hours, 72 hours, and the final day of treatment. They will be performed at external laboratories. A daily headache diary will be used for all patients and they will be given instructions how to use one prior to discharge. A depression screening will be performed on day of admission to TJUH.

Follow-up office visits at approximately 2 weeks and 2 months will be used for collection of pain ratings and medication use. Headache diaries will be collected. If telephone visits occur, assessments will be done over the phone in place of an office visit.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: No masking
• Primary Purpose: Treatment
• Official Title: Ketamine for Refractory Chronic Migraine: a Pilot Study
• Actual Study Start Date: March 22, 2019
• Actual Primary Completion Date: January 1, 2020
• Actual Study Completion Date: January 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment Arm; Patients will be admitted to the hospital for a total of 5 full days from the time of admission until discharge. Ketamine infusion will be started on day 1. Adjustments to ketamine infusion will be made according to standard acute pain service protocol.	Drug: ketamine infusion; Ketamine will be used in subanesthetic doses for patients with refractory chronic migraine to see if it improves pain after a 5-day continuous infusion.; Other Name: Ketalar

Outcome Measures

Primary Outcome Measures :

1. The improvement in pain after ketamine (0 to 10 numerical rating scale) will be compared to improvement after initial inpatient treatment. [ Time Frame: 1 year ]
   Each patient will serve as his or her own control.
2. Improvement in a 0-3 qualitative scale where 0=none, 1=mild, 2=moderate, 3=severe pain will be used comparing change from beginning to end of ketamine treatment to change after initial inpatient treatment. [ Time Frame: 1 year ]
   Each patient will serve as his or her own control.

Secondary Outcome Measures :

1. Incidence of adverse effects [ Time Frame: 1 year ]
   The number and severity of adverse effects, including hallucinations, nightmares, nausea/vomiting, blurry vision, sedation, and changes in liver function tests, will be recorded.
2. Ketamine metabolite levels [ Time Frame: 1 year ]
   Levels of ketamine metabolites, including norketamine, hydroxynorketamines, hydroxyketamines, and dehydronorketamines, will be measured at baseline, 24 h, 48 h, 72 h, and just before infusion is stopped.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• All adult patients (age 18 years and older) who meet the criteria of refractory chronic migraine as defined by the International Classification of Headache Disorders-II definition who present to the Jefferson Headache Center after failing an inpatient course of treatment at Methodist.

Exclusion Criteria:

• Schizophrenia
• active psychosis
• pregnancy
• poorly controlled cardiovascular disease
• cirrhosis
• previous treatment with intravenous ketamine

These criteria are all consistent with the 2018 Consensus Guidelines for Ketamine. Patients who are deemed poor candidates for ketamine by a study team member for any reason, such as intolerance of prior neuroleptic medications, may be excluded.

Contacts and Locations

Locations

United States, Pennsylvania

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Thomas Jefferson University

More Information

Publications:

Schwenk ES, Dayan AC, Rangavajjula A, Torjman MC, Hernandez MG, Lauritsen CG, Silberstein SD, Young W, Viscusi ER. Ketamine for Refractory Headache: A Retrospective Analysis. Reg Anesth Pain Med. 2018 Nov;43(8):875-879. doi: 10.1097/AAP.0000000000000827.

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.

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.

Schulman E. Refractory migraine - a review. Headache. 2013 Apr;53(4):599-613. doi: 10.1111/head.12047. Epub 2013 Feb 13.

Afridi SK, Giffin NJ, Kaube H, Goadsby PJ. A randomized controlled trial of intranasal ketamine in migraine with prolonged aura. Neurology. 2013 Feb 12;80(7):642-7. doi: 10.1212/WNL.0b013e3182824e66. Epub 2013 Jan 30.

Pomeroy JL, Marmura MJ, Nahas SJ, Viscusi ER. Ketamine Infusions for Treatment Refractory Headache. Headache. 2017 Feb;57(2):276-282. doi: 10.1111/head.13013. Epub 2016 Dec 27.

• Responsible Party: Eric Schwenk, Associate Professor, Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT03896256
• Other Study ID Numbers: 19D0.99
• First Posted: March 29, 2019
• Last Update Posted: March 11, 2020
• Last Verified: March 2020

• 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

Additional relevant MeSH terms:

Migraine Disorders; Headache; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action