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

• INCLUSION CRITERIA:
• 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;
• 18-70 years of age at the time of signing the informed consent form;
• Participants may be NIH employees/staff (see below for some exclusion);
• 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.
• Individuals of non-childbearing potential; as defined by the following criteria:
• Postmenopausal defined as 12 months of spontaneous amenorrhea or follicle-stimulating hormone (FSH) serum level > 40 mIU/mL;. appropriate documentation is required.
• Surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriate documentation of surgical procedure.
• Has a congenital condition resulting in no uterus. OR
• Is sterile
• Has documentation confirming vasectomy

EXCLUSION CRITERIA

• 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