A Proof-of-Concept Trial on the Effect of Ketamine on Fatigue

Fatigue Clinical Trial

Official title: A Proof-of-Concept Trial on the Effect of Ketamine on Fatigue

Status Recruiting

Clinical Trial Summary

Background: Many people experience fatigue as a side effect of their illnesses and treatments. There are no medicines to treat fatigue, but a drug called ketamine has reduced fatigue in depressed people. Researchers hope that ketamine, compared to a drug called midazolam, can reduce fatigue in people with illnesses. Objective: To test whether ketamine reduces fatigue in cancer survivors and people with chronic illness. Eligibility: Adults between the ages of 18 and 70 who have fatigue and are cancer survivors or have been diagnosed with a chronic illness such as chronic fatigue syndrome and lupus. Design: Participants will be screened with a physical exam, medical history, blood and urine tests, questions about their fatigue, and breathalyzer test. During phase 1, participants will complete rating their fatigue using questionnaires. They will be provided thinking, memory, and motivation tests. They will also take a handgrip test. For this study, the participant will have an IV, which a needle guides a thin plastic tube (intravenous or IV line) into an arm in their vein. An IV will be required for two of the visits. They will get a single dose of either ketamine or midazolam through an IV line over 40 minutes. Participants must be accompanied by a responsible friend/family/colleague to take them home after getting the study drug. Participants will have follow-up visits where they repeat the above tests. They will also have follow-up phone calls. Phase 2 is the same as phase 1, but participants get the other study drug. The study lasts 1 month. Each phase lasts 2 weeks. Participants will have 6-8 total NIH visits. For the whole study, they will wear a device on their wrists that records physical activity. Drug side effects can include vivid dreams, seeing colors, perceiving time as moving slower or faster than normal, dizziness, headache, restlessness, nausea, or vomiting, among others.

Clinical Trial Description

Purpose: The purpose of the study is to investigate the anti-fatigue effects of ketamine in individuals with chronic illness. Background: Although the underlying mechanisms of fatigue have been studied in several disease conditions, the etiology, mechanisms, and risk factors remain elusive and this symptom remains poorly managed. Fatigue is conceptualized as a multidimensional symptom which incorporates temporal, sensory, cognitive/mental, affective/emotional, behavioral, and physiological dimensions. It is described as a common, chronic, and disabling symptom in individuals with Sjogren s syndrome and those with systemic lupus erythematosus. We recently observed that upregulation of glutamate receptors (e.g.,GRM5) can predict individuals who will develop chronic fatigue one year after completing cancer therapy, suggesting that fatigue may share common glutamatergic markers with depression. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist and has been reported to have rapid anti-depressant effects, and we recently found that it also has rapid anti-fatigue effects. Evidence suggest that severe fatigue in diverse medical conditions is driven by similar biological mechanisms, hence identifying a potential anti-fatigue agent in one medical condition may be a valuable anti-fatigue therapy for other fatiguing conditions. Population for Study: This proof-of-concept study will enroll 59 individuals (target n of completers = 50) with chronic fatigue. Key Inclusion/Exclusion Criteria: Participants must have a fatigue visual analog scale (VAS) score of greater than or equal to 50 mm (on a 0-100 mm horizontal scale). The greater than or equal to 50 mm fatigue VAS score is considered clinically important fatigue cutoff score for patients with chronic illness, and also captures the effectivity outcome of a previous pharmacologic intervention for fatigue. The participants must not have any progressive or unstable conditions or be taking medications that cause fatigue. Methodology: This is a phase II, randomized, double-blind (study team and participants), active comparator-controlled, cross-over trial. After determining eligibility during the screening visit, the participant will be randomized to determine the sequence of study drug/active comparator to take during each phase. Main Study Events / Estimates of Duration and Time Commitments: The study has two periods, and each period is approximately two weeks long (total of four weeks). The study (both periods, excluding the screening visit) will require eight NIH outpatient visits and three phone calls. Primary and Representative Secondary Outcomes: The primary outcome measure of the study is the change in self-reported fatigue VAS score before and three days after receiving ketamine or active comparator (midazolam). A 20% decrease in fatigue VAS score three days after ketamine treatment will be considered the primary indicator of efficacy in this study. The secondary outcomes of this study include: symptoms, physical activity count, skeletal muscle strength, motivation score, cognitive function test scores, changes in gene expression or protein levels of pro-inflammatory markers (e.g., lymphotoxin, IFNy, TNF alpha) typically seen in fatigue, and neurometabolite (e.g., BDNF) levels and mitochondrial markers (e.g., glucose transporter 4) before and after a dose of ketamine or active comparator. General Analytic Plans: A linear mixed model with restricted maximum likelihood estimation will be used to examine changes in fatigue symptoms over the course of the trial where all participants with at least a pre-dose and one post-dose measure will be included. Within-subjects factors will include time with pre-dose and all other points. The interaction between time and ketamine treatment will be included along with the fixed intercept. Multiple test corrections (e.g., Bonferroni post hoc tests) will be used to examine differences between levels of significant effects. The primary outcome measure of the study is the change in fatigue score as measured by the self-reported fatigue instrument. ;

Related Conditions & MeSH terms

• Fatigue

• NCT number: NCT04141696
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Alexander Ross, R.N.
• Phone: (301) 841-5068
• Email: alexander.ross2@nih.gov
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 26, 2021
• Completion date: December 29, 2024