110 Participants Needed
Johns Hopkins University logo

Ketamine for Multiple Sclerosis Fatigue

(INKLING-MS Trial)

Recruiting in Baltimore (>99 mi)
LV
Overseen ByLauren Vega, BSN
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Johns Hopkins University
Must be taking: Fatigue medications
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

You can continue taking your current medication for fatigue if it's not one of the disallowed therapies. You must have been on a stable dose for at least four weeks before the trial and be willing to keep the same dose during the study.

Is there any evidence that the drug ketamine can help with fatigue in multiple sclerosis?

While there is no direct evidence from the provided research about ketamine's effectiveness for multiple sclerosis fatigue, ketamine has been studied for its effects on depression, which is often linked to fatigue in MS. Additionally, other treatments like vitamin B12 have shown some promise in reducing fatigue in conditions similar to MS, suggesting that exploring different treatments for fatigue could be beneficial.12345

Is ketamine safe for human use?

The provided research articles do not contain relevant safety information about ketamine or its various names for human use.678910

How does the drug ketamine differ from other treatments for multiple sclerosis fatigue?

Ketamine is unique because it is primarily known for its rapid-acting antidepressant effects and its use as an anesthetic, which may offer a novel approach to managing fatigue in multiple sclerosis by potentially affecting brain chemistry differently than traditional treatments.1112131415

Research Team

BN

Bardia Nourbakhsh, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for ambulatory adults aged 18-65 with Multiple Sclerosis (MS) who suffer from fatigue as a main symptom. They must meet specific MS diagnostic criteria, have stable health, and be on a consistent dose of any current fatigue medication. Exclusions include severe depression, active cancer treatment, certain heart or liver conditions, substance abuse within the last year, and allergies to ketamine or midazolam.

Inclusion Criteria

Subject must have internet and email access and ability to use a computer or tablet or smartphone
Subject must meet McDonald 2017 diagnostic criteria for multiple sclerosis based on the PI review of the medical records
I can walk at least 20 feet with some help.
See 4 more

Exclusion Criteria

I am currently receiving treatment for cancer.
Breastfeeding or pregnant
Clinically unstable medical or psychiatric disorders that require acute treatment as determined by the PI
See 12 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive infusions of ketamine or midazolam according to their assigned group, with infusions four weeks apart

8 weeks
2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Ketamine
Trial OverviewThe study tests low-dose intravenous ketamine against an active placebo (midazolam) for treating MS-related fatigue. It's phase II, randomized (participants are randomly assigned to one of the two treatments), double-blind (neither participants nor researchers know who gets which treatment), and involves parallel groups where each group receives different treatments.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Midazolam-KetamineExperimental Treatment2 Interventions
Participants in this arm will receive one infusion of midazolam followed four weeks later by an infusion of ketamine.
Group II: Ketamine-MidazolamExperimental Treatment2 Interventions
Participants in this arm will receive one infusion of ketamine followed four weeks later by an infusion of midazolam.
Group III: Ketamine-KetamineExperimental Treatment1 Intervention
Participants in this arm will receive two infusions of ketamine four weeks apart.

Ketamine is already approved in United States, European Union, Canada for the following indications:

๐Ÿ‡บ๐Ÿ‡ธ
Approved in United States as Ketalar for:
  • Anesthesia
  • Treatment-resistant depression
๐Ÿ‡ช๐Ÿ‡บ
Approved in European Union as Ketalar for:
  • Anesthesia
  • Treatment-resistant depression
๐Ÿ‡บ๐Ÿ‡ธ
Approved in United States as Spravato for:
  • Treatment-resistant depression
๐Ÿ‡ช๐Ÿ‡บ
Approved in European Union as Spravato for:
  • Treatment-resistant depression
๐Ÿ‡จ๐Ÿ‡ฆ
Approved in Canada as Spravato for:
  • Treatment-resistant depression

Find a Clinic Near You

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials
2,366
Recruited
15,160,000+

United States Department of Defense

Collaborator

Trials
940
Recruited
339,000+

Findings from Research

Depression and chronic fatigue are equally common in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS), and these two conditions are strongly correlated.
Treatment with levocarnitine did not show any beneficial effects on depression or fatigue in patients with low serum carnitine levels, suggesting that this intervention may not be effective for these symptoms in NMO.
Depressive state and chronic fatigue in multiple sclerosis and neuromyelitis optica.Akaishi, T., Nakashima, I., Misu, T., et al.[2015]
N-acetyl cysteine (NAC) was found to be well-tolerated in individuals with progressive multiple sclerosis (MS), with a high adherence rate of 94%, and a similar incidence of adverse events compared to placebo (60% vs. 80%).
While NAC did not significantly reduce fatigue compared to placebo (mean improvement of 11 points on NAC vs. 18 points on placebo), it did not show a meaningful impact on oxidative biomarkers, suggesting that the dosing or administration method may need to be reconsidered.
A pilot study of oxidative pathways in MS fatigue: randomized trial of N-acetyl cysteine.Krysko, KM., Bischof, A., Nourbakhsh, B., et al.[2022]
In a pilot study of 51 ME/CFS patients, nasal vitamin B12 drops significantly increased serum vitamin B12 levels and improved physical activity, with two-thirds of participants reporting a positive response to treatment.
The treatment led to a notable decrease in fatigue levels as measured by the CIS20r fatigue scale, suggesting that nasal B12 drops could be an effective alternative to injections for managing symptoms in ME/CFS patients.
Open Trial of Vitamin B12 Nasal Drops in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison of Responders and Non-Responders.van Campen, CLM., Riepma, K., Visser, FC.[2020]

References

Depressive state and chronic fatigue in multiple sclerosis and neuromyelitis optica. [2015]
A pilot study of oxidative pathways in MS fatigue: randomized trial of N-acetyl cysteine. [2022]
Open Trial of Vitamin B12 Nasal Drops in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison of Responders and Non-Responders. [2020]
Fatigue associated with multiple sclerosis: diagnosis, impact and management. [2022]
Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia. [2018]
Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. [2022]
The effects of GSK2981710, a medium-chain triglyceride, on cognitive function in healthy older participants: A randomised, placebo-controlled study. [2020]
K.Vita: a feasibility study of a blend of medium chain triglycerides to manage drug-resistant epilepsy. [2022]
LC-MS/MS method for quantification of raspberry ketone in rat plasma: application to preclinical pharmacokinetic studies. [2023]
Effect of Raspberry Ketone on Normal, Obese and Health-Compromised Obese Mice: A Preliminary Study. [2021]
Ketone Ester Supplementation Improves Some Aspects of Cognitive Function during a Simulated Soccer Match after Induced Mental Fatigue. [2023]
12.United Statespubmed.ncbi.nlm.nih.gov
Intracerebroventricular administration of ฮฑ-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats. [2018]
13.United Statespubmed.ncbi.nlm.nih.gov
Imaging cerebral 2-ketoisocaproate metabolism with hyperpolarized (13)C magnetic resonance spectroscopic imaging. [2021]
14.United Statespubmed.ncbi.nlm.nih.gov
High branched-chain alpha-keto acid intake, branched-chain alpha-keto acid dehydrogenase activity, and plasma and brain amino acid and plasma keto acid concentrations in rats. [2018]
15.United Statespubmed.ncbi.nlm.nih.gov
Branched chain keto-acids exert biphasic effects on alpha-ketoglutarate-stimulated respiration in intact rat liver mitochondria. [2018]