Ketamine for Multiple Sclerosis Fatigue

NCT05378100 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB00322473
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is a single-center, phase II, randomized, double-blind, parallel-group, active-placebo-controlled trial of intravenous low-dose ketamine in patients with MS fatigue.

Conditions

Multiple Sclerosis Fatigue

Outcome Measures

Primary Outcomes (1)

• Modified Fatigue Impact Scale (MFIS) Score

  The total score of the MFIS ranges from 0 to 84. Higher scores denote more severe fatigue.

  Baseline (infusion visit) through four weeks after the infusion.

Secondary Outcomes (3)

• Fatigue Severity Scale (FSS)

  Baseline (infusion visit) through four weeks after the infusion.

• Epworth Sleepiness Scale (ESS)

  Baseline (infusion visit) through four weeks after the infusion.

• Beck Depression Inventory-II (BDI-II)

  Baseline (infusion visit) through four weeks after the infusion.

Study Arms (3)

Ketamine-Ketamine

EXPERIMENTAL

Participants in this arm will receive two infusions of ketamine four weeks apart.

Drug: Ketamine

Ketamine-Midazolam

EXPERIMENTAL

Participants in this arm will receive one infusion of ketamine followed four weeks later by an infusion of midazolam.

Drug: Ketamine; Drug: Midazolam

Midazolam-Ketamine

EXPERIMENTAL

Participants in this arm will receive one infusion of midazolam followed four weeks later by an infusion of ketamine.

Drug: Ketamine; Drug: Midazolam

Interventions

Ketamine DRUG

Infusion of ketamine 0.5 mg/kg over 40 minutes

Ketamine-Ketamine; Ketamine-Midazolam; Midazolam-Ketamine

Midazolam DRUG

Infusion of midazolam 0.05 mg/kg over 40 minutes

Ketamine-Midazolam; Midazolam-Ketamine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be a man or woman, 18 to 65 years of age, inclusive.
• Subject must be medically stable based on physical examination, medical history, and vital signs
• Subject must meet McDonald 2017 diagnostic criteria for multiple sclerosis based on the PI review of the medical records
• Subject must complain from fatigue as one of their main symptoms and have a screening MFIS score equal or higher than the cutoff based on gender, age, and education displayed in Table-226
• Subject must be ambulatory (able to walk at least 20 feet using bilateral assistance)
• Subject must have internet and email access and ability to use a computer or tablet or smartphone
• Subjects that are currently taking medication for alleviating fatigue (such as amantadine, modafinil and armodafinil, and amphetamine-like psychostimulants) at Screening are eligible to participate unless the medication is one of the disallowed therapies (Table 3). Subjects taking a fatigue medication at the Screening visit must have been receiving a stable dose for at least four weeks before the Screening visit and be willing to continue the medication at the same dose for the duration of the study.

You may not qualify if:

• BDI-II score of more than 29 (indicating severe depression)
• Having a known clear cause for secondary fatigue, such as untreated sleep apnea, untreated hypothyroidism, chronic liver disease, history of moderate to severe anemia (hemoglobin concentration of less than 9 gr/dl in men or less than 8 gr/dl in women).
• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• United States Department of Defense: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Interventions

Ketamine; Midazolam

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Bardia Nourbakhsh, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2022
• First Posted: May 18, 2022
• Study Start: January 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

US (1)