|First Submitted Date ICMJE||December 14, 2011|
|First Posted Date ICMJE||December 26, 2011|
|Last Update Posted Date||September 11, 2017|
|Start Date ICMJE||February 2013|
|Primary Completion Date||September 2016 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Change in Fatigue Severity Score [ Time Frame: From baseline to the end of four weeks of treatment ]
Change in Fatigue Severity Score from baseline to end of four weeks of treatment
|Original Primary Outcome Measures ICMJE
||Fatigue Severity Scale Score [ Time Frame: Particpants will be treated for 6 weeks ]
We hypothesiizedis that a standardized American gisneng formulation will improved HIV-related fatigue. To test this hypothesis we propose a 6-week double-blind, placebo- controlled trial of 3 escalating doses of American ginseng (1000, 2000, and 3000 mg/day) in 120 HIV+ patients with clinically significant fatigue, as defined by their scores on the Fatigue Severity Scale
|Change History||Complete list of historical versions of study NCT01500096 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||American Ginseng to Improve HIV-Associated Fatigue: A Randomized, Placebo-Controlled, Parallel Design, Multiple-Dose Clinical Trial|
|Official Title ICMJE||American Ginseng to Improve HIV-Associated Fatigue: A Randomized, Placebo-Controlled, Multiple-Dose Escalation Clinical Trial|
|Brief Summary||The purpose of this study is to determine whether American ginseng is effective in the treatment of HIV-associated fatigue.|
STUDY DESIGN Chronic fatigue is a major problem for HIV-infected patients and contributes to decreased quality of life and physical functioning, higher levels of psychological distress, and antiretroviral non-adherence. The etiology of fatigue in HIV-infected patients is unknown, but changes in systemic inflammation may play a contributing role. The mechanism of action of ginseng in the treatment of fatigue is also not clear, but in its role as a purported "adaptogen," it may decrease fatigue by altering systemic inflammation. Ginseng is one of the most popular botanical products in the US and is marketed to improve fatigue and vitality. Our preliminary data suggested that American ginseng at 1000-2000 mg/day may decrease fatigue in cancer patients. HIV-infected patients frequently use ginseng, in part because they perceive these therapies to be safer than more conventional therapies.
We hypothesized that a standardized American ginseng formulation will improved HIV-related fatigue. To test this hypothesis we propose a 6-week double-blind, placebo-controlled trial, parallel study of four weeks of treatment involving two doses of American ginseng or placebo (1000mg/day or 3000 mg/day) in 120 HIV-infected patients with clinically significant fatigue, as defined by their scores on the Fatigue Severity Scale. Patients will be treated with American ginseng or placebo every morning for a total of two doses of 1000 mg/day or 3000 mg/day. A smaller cohort of 12 out of 120 subjects will be enrolled initially to monitor closely for confirmed virologic failure, If confirmed virologic failure is not observed, enrollment will continue to the proposed 120 subjects. Virologic failure is defined as two consecutive plasma viral loads >200 cells according to the 2012 Department of Health Humans Services Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents
The proposed doses of American ginseng are the same as those used in our previous trials. American ginseng 1000 mg/day showed efficacy in ameliorating fatigue in cancer patients. The highest dose of American ginseng (3000 mg/day) selected for this study was derived from our previous American ginseng trial.
Change on scores of the Fatigue Severity Scale (FSS) between American ginseng and placebo groups at baseline, and treatment weeks 2, 4, and 6 (the last safety visit two weeks after completing the 4-week treatment period with American ginseng or placebo) will be calculated. The primary comparison of interest will involve the primary endpoint of the average change in the FSS scale score from baseline to the end of treatment. Other instruments to supplement the FSS and further assess fatigue will be a modified version of the Brief Fatigue Inventory (BFI), The Epworth Sleepiness Scale (ESS), the Patient Health Questionnaire (PHQ-9), Insomnia Severity Index (ISI), the Medical Outcomes Study HIV Health Survey (MOS-HIV), the Clinical Global Impressions (CGI) of Change Scale, and Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue. To further elucidate the mechanism of HIV-related fatigue, we will evaluate the effects of American ginseng and placebo on markers of systemic inflammation such as IL-6 and soluble receptors of tumor necrosis factor (TNF) α 1 and 2 (sTNFR1 and sTNFR2), at baseline and weeks 2, 4, and 6. cluster of differentiation 4 (CD4) cell counts, plasma HIV RNA levels, and adverse events (AEs) will also be assessed for safety purposes.
The total duration of this study is 6 weeks. Participants will receive American ginseng or placebo during the first 4 weeks of the study. On week 6 participants will complete their final post treatment safety study visit.
POPULATION AND SAMPLE SIZE:
120 HIV-infected subjects (40 in the American ginseng 1000 mg/day arm, 40 in the American ginseng 3000 mg/day arm, 20 in the placebo 1000 mg/day arm, and 20 in the placebo 3000 mg/day arm).
This is a randomized, placebo-controlled, longitudinal, parallel study with two doses of American ginseng. As shown in the study schematic figure, two doses of American ginseng or placebo (1000 or 3000 mg/day) will be given to 120 HIV-infected patients (40 in the American ginseng 1000 mg/day arm, 40 in the American ginseng 3000 mg/day arm, 20 in the placebo 1000 mg/day arm, and 20 in the placebo 3000 mg/day arm) with clinically significant fatigue. Participants will receive American ginseng or placebo for a total of 4 weeks and will be followed for a total of 6 weeks (week 6 is the last safety visit 2 weeks after completing the 4-week treatment period with American ginseng or placebo).
American ginseng will be continued for Grades 1 and 2 toxicities at the discretion of the investigator. Treatment will be discontinued for subjects experiencing any grade ≥3 study drug toxicity. Evaluations for the early termination visit will be completed for these subjects. Participants who discontinue treatment secondary to toxicity will be followed until resolution, return to baseline values, or an adequate explanation can be given for their condition. Subjects requiring dose modifications/reductions/interruptions of American ginseng/placebo to manage toxicities will be followed off study drugs. The total number of patients accrued hence will be 120 patients (40 in the American ginseng 1000 mg/day arm, 40 in the American ginseng 3000 mg/day arm, 20 in the placebo 1000 mg/day arm, and 20 in the placebo American ginseng 3000 mg/day arm).
STUDY DURATION The total duration of this study is six weeks. Participants will receive American ginseng or placebo during the first 4 weeks of the study. On week 6 participants will complete their final post treatment safety study visit.
STUDY AGENT/INTERVENTION DESCRIPTION Two doses of American ginseng or placebo (1000 mg/day or 3000 mg/day) every morning by mouth for a 4-week period.
PRIMARY AND SECONDARY OBJECTIVES The overall objective of this study is to determine the effect of American ginseng on fatigue in HIV-infected subjects. HIV-infected subjects with fatigue will be randomized to receive two doses (1000 mg/day or 3000 mg/day) of standardized American ginseng or placebo, and their levels of fatigue and quality of life will be assessed. We will also quantify proinflammatory cytokines in the placebo and American ginseng-treated groups to further elucidate the mechanism of HIV-related fatigue, and the effects of American ginseng on these markers.
Primary Endpoint: Change in FSS total score from baseline to end of four weeks of treatment.
Secondary Endpoints: Change from baseline and values observed at 2, 4, and 6 weeks post-baseline for the following measures: BFI-global assessment score ESS score PHQ-9 total score ISI score MOS-HIV scale total score, Gene Importance Calculator (GIC) score PROMIS fatigue scale score Serum cytokines (IL-6, sTNFR1, sTNFR2) CD4 cell counts, proportion with detectable plasma HIV RNA, AEs will be measured using the Division of AIDS Table for Grading the Severity of Adults Adverse events.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Condition ICMJE||HIV/AIDS-associated Fatigue|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||September 2016|
|Primary Completion Date||September 2016 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01500096|
|Other Study ID Numbers ICMJE||5R01AT005526-03( U.S. NIH Grant/Contract )|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Johns Hopkins University|
|Study Sponsor ICMJE||Johns Hopkins University|
|Collaborators ICMJE||National Center for Complementary and Integrative Health (NCCIH)|
|Investigators ICMJE||Not Provided|
|PRS Account||Johns Hopkins University|
|Verification Date||September 2017|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP