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

NCT04141696 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 20000320-NR-0003
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Fatigue

Keywords

Supportive care; Symptom science; Midazolam; Physiological Effects of Ketamine

Outcome Measures

Primary Outcomes (1)

• Percentage Change in Self-reported Fatigue Visual Analog Scale (VAS) Scale

  Percentage change in self-reported Fatigue Visual Analog Scale (VAS) after a single intravenous dose of the study drug. The Fatigue VAS is a 0-100 mm scale widely used to assess fatigue in patients with chronic illness. Higher score indicates worse fatigue. Change in fatigue VAS scores measured as comparison of fatigue VAS scores collected at the first visit (baseline) and three days post infusion of study drug during each treatment arm (Ketamine, active comparator). Analysis is measured as the difference between day three score minus the baseline score, divided by the baseline score.

  Baseline to three days post infusion for each study arm

Secondary Outcomes (10)

• Percentage Change in Self-reported Fatigue Visual Analog Scale (VAS) Scale - Day 7

  Up to 7 days post infusion for each study drug

• Areas Under the Curve (AUC) for Percentage Changes in Self-reported Fatigue VAS Score - Through Day 7

  Up to 7 days post infusion for each study drug

• Mean Physical Activity Count Using Actigraphy

  Day 7 post infusion

• Fatigue Level Measured by Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale

  Day 7 post infusion

• Patient Reported Outcome Measurement Information System (PROMIS) - Anxiety Domain

  Day 7 post infusion

Study Arms (2)

Ketamine then midazolam administration

EXPERIMENTAL

Participants receive ketamine 0.5 mg/kg intravenous infusion over 40 minutes followed by a two week washout period then receive midazolam 0.045 mg/kg intravenous infusion over 40 minutes followed by two weeks of observation.

Drug: Ketamine; Drug: Midazolam

Midazolam then ketamine administration

ACTIVE COMPARATOR

Participants receive midazolam 0.045 mg/kg intravenous infusion over 40 minutes followed by a two week washout period then receive ketamine 0.5 mg/kg intravenous infusion over 40 minutes followed by two weeks of observation.

Drug: Ketamine; Drug: Midazolam

Interventions

Ketamine DRUG

Given intravenously over 40 minutes

Also known as: Ketalar

Ketamine then midazolam administration; Midazolam then ketamine administration

Midazolam DRUG

Used as placebo comparator; given intravenously over 40 minutes

Also known as: Versed

Ketamine then midazolam administration; Midazolam then ketamine administration

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have chronic, persistent fatigue for at least 6 months;
• Intensity greater than or equal to 50 mm using fatigue VAS (on a 0-100 mm horizontal fatigue scale).
• Chronicity greater than or equal to six months total in the past year using the first item of the revised Piper Fatigue Scale.
• Be a cancer survivor with a documented medical report of completing primary cancer treatment \> 6 months ago (except hormone and vaccine therapies) OR diagnosed with complex syndromes like ME/CFS, CFS, chronic fatigue, fibromyalgia; OR autoimmune disorder such as systemic lupus erythematosus (SLE), or Sjogren s disease;
• Able to provide written informed consent;
• Able to have an accompanying responsible adult for drug infusion study visits;
• years of age at the time of signing the informed consent form;
• Individuals of childbearing potential must use adequate contraception, as defined below, prior to study entry and for the duration of study participation. Sexually active subjects must agree to use at least one medically accepted barrier method of contraception during the study. For example:
• Condoms
• Prescribed hormonal oral contraceptives, vaginal ring, or transdermal patch.
• Intrauterine device (IUD).
• Intrauterine hormone-releasing system (IUS).
• Depot/implantable hormone (e.g., Depo-provera , Implanon).
• Bilateral tubal occlusion/ligation.
• Sexual abstinence: refraining from intercourse during the entire period of risk associated with the study requirements or if the participant decides to become sexually active during the study, then one of the highly effective birth control methods must be used.

You may not qualify if:

• Total body irradiation or cranial irradiation for cancer;
• Has a diagnosis of progressive or unstable disease to any body system causing clinically significant fatigue (e.g., class IV congestive heart failure, end-stage renal disease, liver failure, stage IV chronic obstructive pulmonary disease) including patients with active systemic infections (e.g., human immunodeficiency virus (HIV), active hepatitis, COVID-19 - screened using NIH Clinical Center questionnaire);
• Individuals with comorbid conditions other than clinically stable cardiovascular, metabolic conditions, and rheumatologic/systemic autoimmune diseases;
• Current or past psychiatric disorders including medically documented depression with psychosis, bipolar disorder, schizophrenia;
• Clinically documented post-traumatic stress syndrome and/or traumatic brain injury because of the high risk for ketamine to exacerbate symptoms including hallucinations;
• Categorized as a high-risk drinker (\>=5 drinks/day and \>=15 drinks/week for men, \>=4 drinks/day and \>=8 drinks/week for women). ("Dietary Guidelines for Americans 2015-2020," U.S. Department of Health and Human Services and U.S. Department of Agriculture);
• Detectable alcohol content \>1 mg/dL using either breath test or using other biologic samples (e.g., urine);
• Current substance use disorder within the last five years as diagnosed on the Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)-5 (SCID-5) or positive urine toxicology results at enrollment;
• Participants with clinical hypothyroidism or hyperthyroidism defined by abnormal thyroid stimulating hormone (TSH);
• Poorly controlled hypertension as judged by the Principal Investigator and confirmed by repeat assessment during the screening period (systolic blood pressure (SBP) \>160 and diastolic blood pressure (DBP) \> 100 in all readings);
• Any medical condition causing impairment in mobility (e.g., stroke with residual neuromuscular weakness). This may prohibit the assessment of study outcomes, such as physical activity;
• Any change in dose of regularly scheduled medication or initiation of a new medication (excluding PRN medications) within four weeks prior to signing the informed consent form and throughout the entire duration of the study;
• Untreated sleep condition.
• Medically diagnosed kidney disease (except for chronic stable kidney disease with eGFR\>45);
• Medically diagnosed acute narrow-angle glaucoma;

Sponsors & Collaborators

• National Institute of Nursing Research (NINR): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Saligan LN, Luckenbaugh DA, Slonena EE, Machado-Vieira R, Zarate CA Jr. An assessment of the anti-fatigue effects of ketamine from a double-blind, placebo-controlled, crossover study in bipolar disorder. J Affect Disord. 2016 Apr;194:115-9. doi: 10.1016/j.jad.2016.01.009. Epub 2016 Jan 19.

  PMID: 26807672 BACKGROUND

• Sharpe M, Wilks D. Fatigue. BMJ. 2002 Aug 31;325(7362):480-3. doi: 10.1136/bmj.325.7362.480. No abstract available.

  PMID: 12202331 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Fatigue

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Leorey Saligan, PhD.
• Organization: National Institute of Nursing Research (NINR)

saliganl@mail.nih.gov

+1 301 451 1685

Study Officials

• Leorey N Saligan, C.R.N.P.

  National Institute of Nursing Research (NINR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: October 28, 2019
• Study Start: July 26, 2021
• Primary Completion: March 21, 2024
• Study Completion: March 21, 2024
• Last Updated: April 15, 2025
• Results First Posted: April 15, 2025

Record last verified: 2025-02-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: Publicly available after closure of the study
• Access Criteria: De-identified data

Locations

US (1)