Ketamine for MS Fatigue

Multiple Sclerosis Clinical Trial

Official title:

A Pilot Study of Intravenous, Subanesthetic Dose of Ketamine Versus Placebo, A Crossover Design, for Multiple Sclerosis Related Fatigue

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06064162
• Other study ID #: REDI2022MS
• Status: Recruiting
• Phase: Early Phase 1
• Start date: December 5, 2023
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Alta Bates Summit Medical Center
• Contact: Deepak Soneji, MD
• Phone: 510.204.8140
• Email: Deepak.Soneji[@]sutterhealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to see whether using ketamine to increase glutamate in the prefrontal cortex can reduce Multiple Sclerosis (MS) related fatigue. The investigator proposes a prospective, crossover, randomized, placebo-controlled study to assess the efficacy and safety of low, single dose Ketamine, to assess its efficacy and safety in patients with MS-related fatigue.

Description:

The study treatment is designed in two 28-day cycles: for each cycle, participants will receive study infusion on Day 1 and complete follow-up visits during Days 7 and 28. Participants are randomized 1:1 to receive either ketamine (active treatment) or saline solution (placebo treatment) for their first infusion. They will not be blinded to their study assignment: the study doctor will disclose their assigned treatment group. After their first infusion cycle, participents will crossover to the other treatment group. Worded differently, if a participant received ketamine during their first infusion, they will receive placebo treatment during their second infusion. Conversely, if a participant received saline treatment during their first infusion, they will receive ketamine during their second infusion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Female and Male patients with any form of CDMS ages 18-65 inclusive

2. Report fatigue which is interfering with QOL

3. Able and willing to sign informed consent

4. Stable on DMT for at least 3 months prior to baseline visit

5. Not experiencing an MS relapse within 90 days prior to baseline visit.

6. Must agree to practice an acceptable method of contraception

7. Experiencing significant fatigue due to MS (MFIS of =10)

Exclusion Criteria:

1. Allergy to Ketamine

2. Taking medications which may interact with ketamine

3. Change in DMT within 3 months prior to baseline visit

4. MS relapse within 90 days of the baseline visit

5. Confirmed diagnosis of untreated Sleep Apnea

6. Confirmed diagnosis of periodic limb movement disorder

7. Serious infection in the 30 days prior to baseline visit.

8. Patients with significant comorbid conditions:

1. Untreated hypertension (SBP>160, DBP>100 at baseline)

2. Liver disease

3. Significant renal disease

4. History of cardiac arrhythmia

5. Any comorbidities which at the opinion of the investigators post undue risk

9. Current alcohol or drug abuse

10. Participation in another interventional clinical trial in the past 3 months.

11. Pregnant or lactating

12. Any condition which in the opinion of the investigators will cause safety concerns for the patient, or inability to comply with the protocol.

Related Conditions & MeSH terms

• Fatigue
• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• ketamine
60mg (.5mg/kg over 40 minutes intravenously)

Locations

Country	Name	City	State
United States	Alta Bates Summit Medical Center	Berkeley	California

Sponsors (1)

Lead Sponsor	Collaborator
Alta Bates Summit Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (11)

Asano M, Finlayson ML. Meta-analysis of three different types of fatigue management interventions for people with multiple sclerosis: exercise, education, and medication. Mult Scler Int. 2014;2014:798285. doi: 10.1155/2014/798285. Epub 2014 May 14. — View Citation

Beard C, Hsu KJ, Rifkin LS, Busch AB, Bjorgvinsson T. Validation of the PHQ-9 in a psychiatric sample. J Affect Disord. 2016 Mar 15;193:267-73. doi: 10.1016/j.jad.2015.12.075. Epub 2015 Dec 31. — View Citation

Broicher SD, Filli L, Geisseler O, Germann N, Zorner B, Brugger P, Linnebank M. Positive effects of fampridine on cognition, fatigue and depression in patients with multiple sclerosis over 2 years. J Neurol. 2018 May;265(5):1016-1025. doi: 10.1007/s00415- — View Citation

Fitzgerald KC, Morris B, Soroosh A, Balshi A, Maher D, Kaplin A, Nourbakhsh B. Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis-related fatigue. Mult Scler. 2021 May;27(6):942-953. doi: 10.1177/ — View Citation

Induruwa I, Constantinescu CS, Gran B. Fatigue in multiple sclerosis - a brief review. J Neurol Sci. 2012 Dec 15;323(1-2):9-15. doi: 10.1016/j.jns.2012.08.007. Epub 2012 Aug 27. — View Citation

Kos D, Kerckhofs E, Nagels G, D'hooghe MB, Ilsbroukx S. Origin of fatigue in multiple sclerosis: review of the literature. Neurorehabil Neural Repair. 2008 Jan-Feb;22(1):91-100. doi: 10.1177/1545968306298934. Epub 2007 Apr 4. — View Citation

Meca-Lallana V, Branas-Pampillon M, Higueras Y, Candeliere-Merlicco A, Aladro-Benito Y, Rodriguez-De la Fuente O, Salas-Alonso E, Maurino J, Ballesteros J. Assessing fatigue in multiple sclerosis: Psychometric properties of the five-item Modified Fatigue — View Citation

Nourbakhsh B, Revirajan N, Morris B, Cordano C, Creasman J, Manguinao M, Krysko K, Rutatangwa A, Auvray C, Aljarallah S, Jin C, Mowry E, McCulloch C, Waubant E. Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple scle — View Citation

Saligan LN, Farmer C, Ballard ED, Kadriu B, Zarate CA Jr. Disentangling the association of depression on the anti-fatigue effects of ketamine. J Affect Disord. 2019 Feb 1;244:42-45. doi: 10.1016/j.jad.2018.10.089. Epub 2018 Oct 6. — View Citation

Stankoff B, Waubant E, Confavreux C, Edan G, Debouverie M, Rumbach L, Moreau T, Pelletier J, Lubetzki C, Clanet M; French Modafinil Study Group. Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology. 2005 Apr 12;64(7): — View Citation

Wesson JM, Cooper JA, Jehle LS, Lockhart SN, Draney K, Barber J. The functional index for living with multiple sclerosis: development and validation of a new quality of life questionnaire. Mult Scler. 2009 Oct;15(10):1239-49. doi: 10.1177/1352458509107019 — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improve Fatigue Scores	a statistically significant change in the level of fatigue score as measured by the Multiple Schlerosis fatigue scales: Modified Fatigue Impact Scale (MFIS) between baseline and day 28 post study drug infusion. Rating scale is 0 to 4 with 0 being "never" and 4 being "almost always."	28 days post study drug infusion
Secondary	Improve Quality of Life	A statistically significant change in the patient's quality of life as measured by Functional Index for Living with Multiple Sclerosis (FILMS) between baseline and day 28. Score is rated 1 to 5 with 1 being "bad" and 5 being "good."	Between baseline and day 28

External Links

•   National Multiple Sclerosis Society