Effectiveness of Armodafinil for Treating Fatigue in Adults With HIV/AIDS

Study Overview
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Brief Summary
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This study will determine whether armodafinil (Nuvigil), an FDA approved medication, is effective in reducing fatigue in adults with HIV/AIDS.

Detailed Description
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Fatigue is a common problem for many people with HIV/AIDS, interfering with daily activities and serving as a significant barrier to working among those whose health is otherwise stable or restored by antiretroviral (ARV) medication. Fatigue in HIV is associated with disability and diminished quality of life. It may be caused by ARVs or by the virus itself. A related study tested whether modafinil, of which armodafinil is an r-isomer, could reduce fatigue in HIV/AIDS patients. Armodafinil, believed to have a longer duration and greater effect than modafinil, will be tested on the same criteria. Participants will be randomly assigned to receive either armodafinil or a placebo daily for 4 weeks. Participants randomized to active medication and who show improvements in symptoms will be offered armodafinil for an additional 12 weeks. For them, the study duration is 16 weeks. Participants who did not receive armodafinil will be offered armodafinil for 16 weeks. For these participants, the study duration is 20 weeks. Participants who did not benefit from armodafinil will receive alternate treatment options. All participants will have weekly study visits for the first 4 weeks of the study and biweekly visits for the remainder of the study. At each visit, participants will complete various tasks to determine cognitive function, and self-report scales will be used to determine symptoms of depression and fatigue. After completion of 16 weeks, participants responding to armodafinil will be transitioned to the publicly available modafinil over the course of 2 weeks.

Official Title
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Armodafinil Treatment for Fatigue in HIV+ Patients

Conditions
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HIV Infections, Fatigue

Intervention / Treatment
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* Drug: Armodafinil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18-75 HIV+ Clinically significant fatigue (score of 4.5+ on Fatigue Severity Scale, plus impairment on 1+ categories of Role Function Scale) Fatigue duration for 3+ months English-speaking Able to give informed consent Fecund women uses barrier method of contraception Exclusion Criteria: Primary care doctor does not approve of study participation Unstable medical condition (e.g. liver failure; cirrhosis, new onset opportunistic infection in past month) Untreated hypogonadism, except for men for whom testosterone replacement is medically contraindicated (serum testosterone below the reference range) Untreated hypothyroidism (Thyroid Stimulating Hormone over 5 IUI/mL) Untreated and uncontrolled hypertension Clinically significant anemia (hematocrit <30%) Started testosterone or nandrolone in past 6 weeks Started or changed an antiretroviral regimen in past 4 weeks if fatigue predated the change; otherwise, started or changed regimen in past 2 months Untreated or under-treated major depressive disorder Started antidepressant medication within past 6 weeks Substance abuse/dependence (past 4 months) Regular and frequent cannabis use (> twice/week regularly) Currently clinically significant suicidal ideation or Hamilton Depression Scale (HAM-D) score >24 History or current psychosis or bipolar disorder Pregnant or breastfeeding Significant untreated insomnia (score >3 on HAM-D insomnia items) Currently taking psychostimulant medication or past nonresponse to modafinil Has no alternative viable antiretroviral regimen after the current one Left ventricular hypertrophy; mitral valve prolapse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Armodafinil<br>Participants will take armodafinil for 4 weeks. The dose will be titrated up from 50mg to 250mg per day as clinically indicated, using 50mg tablets. If responsive, participants will be offered 12 additional weeks of armodafinil. | Drug: Armodafinil<br>* Participants will receive 50 mg of armodafinil per day, increasing to 250 mg per day as clinically indicated.<br>* Other names: Nuvigil;|
| Placebo Comparator: Placebo<br>Participants will receive placebo pills for 4 weeks. Placebo tablets that match the 50mg active medication tablets will given following the same dosing strategy as Arm 1. The dose will be titrated from 1 placebo tablet daily to 5 tablets daily as clinically indicated. Non-responders to placebo will then be offered 16 weeks of active medication. | Drug: Placebo<br>* Participants will receive placebo pills matched to the active armodafinil and according to the same dosing strategy<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue Severity Scale(FSS) Outcome | The FSS is a 9-item self-report scale that measures the impact of fatigue on everyday functioning. Each item is rated on a scale of 1 to 7. Total scores range from 9-63, with a higher score indicating greater impairment due to fatigue. | Measured at baseline and Weeks 4 | 
| Role Function Scale | The Role Function Scale includes 10 items drawn from the Short Form 36-item Survey (SF-36) and other SF versions. It is intended to assess the extent to which fatigue has a behavioral impact on daily activities. Scores of frequency in the past week, on a 5-point scale, are summed with higher scores signifying greater role impairment. Scores range from 10-50. | Measured at Baseline and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 Cell Count | Cd4 cell count is a laboratory marker providing an indication of immune system functioning. Blood samples were drawn for this measure at baseline and week 4. The reference range for CD4 cell count is 490-1740, and a clinically significant change is defined as a change of >=100 cells. A higher number is associated with better immune functioning. | Measured at baseline and Week 4 | 
| HIV Viral Load | HIV RNA viral load assay is a laboratory measure indicating viral activity. Because of the large range of possible values (50 - 100,000 copies), this measure is transformed to log10 values. We entered the log10 value of 1.69 when the laboratory result stated under 50 copies, which was the assay's lowest limit of detectability during the study. | Measured at baseline and Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, AIDS, Armodafinil, Depression