Ketamine for Multiple Sclerosis Fatigue (INKLING-MS)

Low-Dose Ketamine Infusion for the Treatment of Multiple Sclerosis Fatigue (INKLING-MS)

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis Fatigue
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lauren Vega, BSN; Phone Number: 410-614-1522; Email: ldimarc2@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
      • Contact: Mahsa Ghajarzadeh, MD, PhD; Email: mghajar2@jhmi.edu
      • Contact: Lauren Vega, BSN; Email: Ldimarc2@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine-Ketamine; Participants in this arm will receive two infusions of ketamine four weeks apart.	Drug: Ketamine; Infusion of ketamine 0.5 mg/kg over 40 minutes
Experimental: Ketamine-Midazolam; Participants in this arm will receive one infusion of ketamine followed four weeks later by an infusion of midazolam.	Drug: Ketamine; Infusion of ketamine 0.5 mg/kg over 40 minutes; Drug: Midazolam; Infusion of midazolam 0.05 mg/kg over 40 minutes
Experimental: Midazolam-Ketamine; Participants in this arm will receive one infusion of midazolam followed four weeks later by an infusion of ketamine.	Drug: Ketamine; Infusion of ketamine 0.5 mg/kg over 40 minutes; Drug: Midazolam; Infusion of midazolam 0.05 mg/kg over 40 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue Severity Scale (FSS)	The total score of the FSS ranges from 1 to 7. Higher scores denote more severe fatigue.	Baseline (infusion visit) through four weeks after the infusion.
Epworth Sleepiness Scale (ESS)	The total score of the ESS ranges from 0 to 24. Higher scores denote more severe sleepiness.	Baseline (infusion visit) through four weeks after the infusion.
Beck Depression Inventory-II (BDI-II)	The total score of the BDI-IIranges from 0 to 63. Higher scores denote more severe depression.	Baseline (infusion visit) through four weeks after the infusion.

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: United States Department of Defense

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: May 12, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 18, 2022

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Fatigue; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: IRB00322473

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After completion of the study and publication of key findings, the study investigators will make Final Research Data available to researchers upon written request. Researchers must adhere to a data sharing agreement. This agreement requires users to:

(1) use the data only for research purposes; (2) not share the data with unauthorized users; (3) ensure that the data are protected from unauthorized persons; (4) require that the data be returned or destroyed at the end of the analysis; (5) provide certification of IRB review and approval.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• 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