American Ginseng to Improve HIV-Associated Fatigue: A Randomized, Placebo-Controlled, Parallel Design, Multiple-Dose Clinical Trial
Condition: HIV/AIDS-associated Fatigue
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Fatigue
Intervention: American ginseng; Placebo for American ginseng
Intervention description: American ginseng 1000 mg/day and 3000 mg/day will be evaluated in the intervention arms for this study. Participants will be randomized to American ginseng 1000 or 3000 mg/day capsules taken daily for four weeks.; Placebo for American ginseng 1000 mg/day and 3000 mg/day will be evaluated in the control arms for this study. Participants will be randomized to placebo for American ginseng 1000 or 3000 mg/day capsules taken daily for four weeks.
Arms: Placebo for American ginseng 1000 mg/day, Placebo for American ginseng 3000 mg/day
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Fatigue; HIV/AIDS; American ginseng; Panax quinquefolius; Fatigue Severity Scale; CD4 count; plasma HIV RNA; cytokines; IL-6; sTNFR1; sTNFR2

Summary:

      The purpose of this study is to determine whether American ginseng is effective in the
      treatment of HIV-associated fatigue.
    

Eligibility criteria:

        INCLUSION CRITERIA

          1. HIV-infected men and women, ≥18 years of age

          2. HIV-1 infection documented by a rapid HIV test or any licensed ELISA test kit and
             confirmed by a repeat ELISA, Western blot at any time prior to study entry; or
             documentation of ongoing HIV/AIDS care, or treatment for AIDS, or previous positive
             HIV serology at any time prior to study entry

          3. On stable antiretroviral therapy for at least three months

          4. Undetectable plasma HIV RNA using conventional assays with lower limits of
             quantification (20-75 copies/ml) obtained within 30 days prior to entry

          5. The following laboratory values obtained within 30 prior to study entry:

             Absolute neutrophil count (ANC) ≥750/mm3 Hematocrit ≥30 Platelet count ≥40,000/mm3
             Calculated creatinine clearance (CrCl) ≥50 mL/min, as estimated by the Cockcroft-Gault
             equation* aspartate amino transferase (AST) serum glutamic oxalacetic transaminase
             (SGOT), amino alanine transferase (ALT) serum glutamic-pyruvic transaminase (SGPT),
             and alkaline phosphatase <3 x upper limit of normal (ULN) total bilirubin ≤2.5 x ULN

             NOTE: If the potential subject is taking an atazanavir-containing regimen at the time
             of screening, total bilirubin ≤5 x ULN is acceptable

             * Calculation for the Cockcroft-Gault equation is available at
             https://www.fstrf.org/common/utilities/calculators/ccc.html

          6. Clinically significant fatigue (≥4.5 on the FSS)

          7. PHQ-9 Questionnaire score <10

          8. ISI Questionnaire <14

          9. On stable psychiatric medications for at least 8 weeks prior to enrollment.

         10. Ability and willingness of subject to provide a signed informed consent and comply
             with all study requirements

         11. Laboratory values and physical examination as judged by the principal investigator to
             be safe to participate

         12. Females of reproductive potential (women who have not been post-menopausal for at
             least 24 consecutive months, i.e., who have had menses within the preceding 24 months,
             or women who have not undergone surgical sterilization, specifically hysterectomy, or
             bilateral oophorectomy or tubal ligation) will need a negative serum or urine
             pregnancy test within 30 days prior to entry.

             NOTE: Acceptable documentation of hysterectomy and bilateral oophorectomy, tubal
             ligation, tubal micro-inserts, and menopause is self-reported history.

         13. All potential subjects must agree not to participate in the conception process (e.g.,
             active attempt to become pregnant or to impregnate, sperm donation, in vitro
             fertilization), and if participating in sexual activity that could lead to pregnancy,
             the subject/ partner must reliable methods of contraception (condoms, with or without
             a spermicidal agent; a diaphragm or cervical cap with spermicide; an intrauterine
             contraceptive device (IUD); or hormone-based contraceptive) while receiving study
             treatment. Subjects will be encourage to use a barrier method of contraception (e.g.
             condoms) along with hormonal contraceptives during administration of American ginseng.

        EXCLUSION CRITERIA

          1. Untreated hypothyroidism (TSH >4.5 milli-international units per liter (mIU/L))

          2. Untreated or undertreated hypogonadism (calculated free testosterone below The lower
             limit of normal)

          3. Untreated or under-treated major depressive disorder

          4. No change in testosterone therapy within 6 weeks prior to screening

          5. As determined by the investigator, history of chronic or acute medical condition that
             in the opinion of the investigator would jeopardize safety of subjects participating
             in this study

          6. Hospitalization or therapy for serious illness within 30 days prior to study entry as
             judged by the investigator

          7. Known allergy/sensitivity or any hypersensitivity to components of American ginseng

          8. Active drug or alcohol use or dependence that, in the opinion of the site
             investigator, would interfere with adherence or subject compliance with study
             requirements (stable methadone treatment allowed)

          9. Current use or requirement for any medications prohibited with study treatment
             including warfarin. (Lists of prohibited medications are contained in the Prohibited
             Medications Section of the protocol)

         10. Pregnancy or breastfeeding

         11. Use of any immunomodulator (e.g., interferons, interleukins, systemic corticosteroids,
             cyclosporine), vaccine, or investigational therapy within 30 days prior to study entry

         12. Treatment with investigational study drugs/vaccines

         13. Co-enrolment in observational trials is allowed if the blood volume requirement does
             not exceed the Red Cross limits specified for this clinical trial