Ketamine for Multiple Sclerosis Fatigue

NCT ID: NCT05378100

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2026-10-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine-Ketamine

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

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

Infusion of ketamine 0.5 mg/kg over 40 minutes

Ketamine-Midazolam

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

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

Infusion of ketamine 0.5 mg/kg over 40 minutes

Midazolam

Intervention Type: DRUG

Infusion of midazolam 0.05 mg/kg over 40 minutes

Midazolam-Ketamine

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

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

Infusion of ketamine 0.5 mg/kg over 40 minutes

Midazolam

Intervention Type: DRUG

Infusion of midazolam 0.05 mg/kg over 40 minutes

Interventions

Ketamine

Infusion of ketamine 0.5 mg/kg over 40 minutes

Intervention Type: DRUG

Midazolam

Infusion of midazolam 0.05 mg/kg over 40 minutes

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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
• Taking any disallowed therapy(ies), as noted in the protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bardia Nourbakhsh, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Lauren Vega, BSN

Role: CONTACT

ldimarc2@jhmi.edu

410-614-1522

Facility Contacts

Mahsa Ghajarzadeh, MD, PhD

Role: primary

mghajar2@jhmi.edu

Lauren Vega, BSN

Role: backup

Ldimarc2@jhmi.edu

Other Identifiers

IRB00322473

Identifier Type: -

Identifier Source: org_study_id