American Ginseng to Improve HIV-Associated Fatigue: A Randomized, Placebo-Controlled, Parallel Design, Multiple-Dose Clinical Trial

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* AST (SGOT), ALT (SGPT), and alkaline phosphatase <3 x 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 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 uIU/ml)
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