Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    ketamine | Multiple Sclerosis
Previous Study | Return to List | Next Study

Ketamine for Treatment of MS Fatigue

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03500289
Recruitment Status : Completed
First Posted : April 18, 2018
Results First Posted : August 4, 2020
Last Update Posted : August 18, 2020
Sponsor:
Collaborator:
National Multiple Sclerosis Society
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

Multiple sclerosis (MS) is an inflammatory, demyelinating and degenerative disease of the central nervous system and, after trauma, is the most common cause of disability in young adults, affecting more than 400,000 individuals in the US. Of all the symptoms that can occur with MS, chronic fatigue is the most common and disabling, reported by at least 75% of patients at some point. Fatigue limits patients' daily activities, and challenges employment, resulting in substantial socioeconomic consequences. Despite this negative impact, fatigue treatments have been inconsistently studied, in part due to poorly understood underlying pathophysiological mechanisms. Yet to be defined biological processes and lack of clear treatment targets have also hampered the development of drugs for fatigue. As a result, there are no medications approved by the Food and Drug Administration (FDA) for the treatment of MS fatigue.

The investigators recently reported that riluzole, a medication with anti-glutamatergic effects, increased the fatigue severity in patients with relapsing MS who had participated in a clinical trial evaluating potential neuroprotective effects of riluzole versus placebo. Three other clinic trials which examined memantine effects on cognition in patient with MS also reported worsening fatigue as a major side effect. Memantine main mechanism of action is blocking the N-methyl D-aspartate (NMDA) glutamate receptor. These observations prompted the investigators that glutamatergic transmission probably plays an important role in fatigue pathogenesis and modulating these pathways could have potential therapeutic effect on MS-related fatigue. A recent paper reported that ketamine, an NMDA receptor blocker with different kinetics compared to memantine, had a strong and prolonged effect in reducing fatigue in bipolar patients who participated in a clinical trial, evaluating anti-depressive effects of ketamine versus placebo. Interestingly, the effect of ketamine on fatigue was independent of its antidepressant effects.

The primary objective of this study is to determine if modulating glutamatergic transmission with ketamine is safe and efficacious in improving MS-related fatigue. These objectives will be answered in a proof of concept, randomized controlled trial of ketamine versus an active placebo (midazolam) in patients with relapsing or progressive MS who have clinically significant fatigue.

18 patients with MS and reported fatigue, will be randomized 2:1 to one infusion of ketamine 0.5 mg/kg over 40 minutes versus one infusion of midazolam 0.05 mg/kg over 40 minutes. Midazolam is chosen as an active placebo to keep the participants blinded to participants' medication assignment. Primary outcome of the study will be Daily Fatigue Severity measured daily from day one through day seven post-infusion.

Secondary outcomes of the study include other fatigue questionnaires, depression and sleepiness. The length of study will be around 28 days.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Fatigue Drug: Ketamine Drug: Midazolam Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Ketamine for Treatment of Multiple Sclerosis-related Fatigue
Actual Study Start Date : August 10, 2018
Actual Primary Completion Date : August 30, 2019
Actual Study Completion Date : August 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ketamine Drug: Ketamine
One intravenous infusion of ketamine 0.5 mg/kg over 40 minutes

Placebo Comparator: Midazolam Drug: Midazolam
One intravenous infusion of midazolam 0.05 mg/kg over 40 minutes




Primary Outcome Measures :
  1. Change in Daily Fatigue Severity Score [ Time Frame: Baseline (infusion visit) through day 7 ]
    It is a single item question: 'how much fatigue (tiredness, weariness, problems thinking clearly) have you felt today?' with responses from 0 'None at all' to 10 'Extreme Fatigue'. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study].


Secondary Outcome Measures :
  1. Change in Quality of Life in Neurological Disorders (NeuroQol) Fatigue Item Bank Score [ Time Frame: Baseline (infusion visit) through day 28 post-infusion ]
    T-score distributions rescale raw scores into standardized scores with a mean of 50 and a standard deviation (SD) of 10. Higher T-scores denote more severe fatigue. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study].

  2. Change in Modified Fatigue Impact Scale (MFIS) Score [ Time Frame: Baseline (infusion visit) through Day 28 post-infusion ]
    The total score of the MFIS ranges from 0 to 84. Higher scores denote more severe fatigue. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study].

  3. Change in Epworth Sleepiness Scale Score [ Time Frame: Baseline (infusion visit) through day 28 post-infusion ]
    The Epworth Sleepiness Scale score can range from 0 to 24. The higher the score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study].

  4. Change in Beck Depression Inventory (BDI) Score [ Time Frame: Baseline (infusion visit) through day 28 post-infusion ]
    The total score of the BDI ranges from 0 to 63. Higher scores denote more severe depressive symptoms. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study].

  5. Change in Fatigue Severity Scale (FSS) Score [ Time Frame: Baseline (infusion visit) through day 28 post-infusion ]
    The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study].



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18 years 65 years.
  • Females of childbearing age must have a negative urine pregnancy test at baseline and use an effective method of contraception during the study.
  • Diagnosis of MS (according to the 2010 McDonald criteria).
  • Ambulatory (at least 20 feet using bilateral assistance).
  • Fatigue reportedly present and screening modified fatigue impact scale (MFIS) score >33.
  • Internet and email access and able to use a computer or tablet

Exclusion Criteria:

  • Beck Depression Inventory (BDI) score of more than 30.
  • Neurodegenerative disorders other than relapsing or progressive MS.
  • Breastfeeding or pregnant.
  • History of coronary artery disease or congestive heart failure.
  • Uncontrolled hypertension at screening (history of high blood pressure and screening systolic blood pressure >160 or diastolic blood pressure>100).
  • History of severe liver disease, including cirrhosis.
  • Terminal medical conditions.
  • Currently treated for active malignancy.
  • Alcohol or substance abuse in the past year (except marijuana or other cannabinoids).
  • A history of intolerance or allergic or anaphylactic reaction to ketamine or midazolam
  • Clinically unstable medical or psychiatric disorders that require acute treatment as determined by the PI.
  • History of severe or untreated coronary artery disease or history of congestive heart failure.
  • History of prior ischemic or hemorrhagic stroke and cerebral vascular aneurysms.
  • History of recurrent seizures or epilepsy.
  • Taking any disallowed therapy(ies) as noted in Appendix 2 of the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03500289


Locations
Layout table for location information
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
National Multiple Sclerosis Society
Investigators
Layout table for investigator information
Principal Investigator: Bardia Nourbakhsh, MD, MAS Johns Hopkins University
  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:
Layout table for additonal information
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03500289    
Other Study ID Numbers: IRB00164017
First Posted: April 18, 2018    Key Record Dates
Results First Posted: August 4, 2020
Last Update Posted: August 18, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for MeSH terms
Multiple Sclerosis
Sclerosis
Ketamine
Fatigue
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Midazolam
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
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs