Ketamine for Multiple Sclerosis Fatigue (INKLING-MS)

Johns Hopkins University

Status and phase: Enrolling; Phase 2

Conditions: Multiple Sclerosis Fatigue

Treatments: Drug: Midazolam; Drug: Ketamine

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT05378100

IRB00322473

Details and patient eligibility

About

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.

Enrollment: 110 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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110 participants in 3 patient groups

Ketamine-Ketamine

Experimental group

Description:

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

Treatment:

Drug: Ketamine

Ketamine-Midazolam

Experimental group

Description:

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

Treatment:

Drug: Ketamine

Drug: Midazolam

Midazolam-Ketamine

Experimental group

Description:

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

Treatment:

Drug: Ketamine

Drug: Midazolam