Fatigue, HIV Infections
Conditions
Keywords
HIV, AIDS, Armodafinil, Depression
Brief summary
This study will determine whether armodafinil (Nuvigil), an FDA approved medication, is effective in reducing fatigue in adults with HIV/AIDS.
Detailed description
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.
Interventions
DRUGArmodafinil
Participants will receive 50 mg of armodafinil per day, increasing to 250 mg per day as clinically indicated.
DRUGPlacebo
Participants will receive placebo pills matched to the active armodafinil and according to the same dosing strategy
Sponsors
National Institute of Mental Health (NIMH)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 18-75 2. HIV+ 3. Clinically significant fatigue (score of 4.5+ on Fatigue Severity Scale, plus impairment on 1+ categories of Role Function Scale) 4. Fatigue duration for 3+ months 5. English-speaking 6. Able to give informed consent 7. Fecund women uses barrier method of contraception
Exclusion criteria
1. Primary care doctor does not approve of study participation 2. Unstable medical condition (e.g. liver failure; cirrhosis, new onset opportunistic infection in past month) 3. Untreated hypogonadism, except for men for whom testosterone replacement is medically contraindicated (serum testosterone below the reference range) 4. Untreated hypothyroidism (Thyroid Stimulating Hormone over 5 IUI/mL) 5. Untreated and uncontrolled hypertension 6. Clinically significant anemia (hematocrit \<30%) 7. Started testosterone or nandrolone in past 6 weeks 8. Started or changed an antiretroviral regimen in past 4 weeks if fatigue predated the change; otherwise, started or changed regimen in past 2 months 9. Untreated or under-treated major depressive disorder 10. Started antidepressant medication within past 6 weeks 11. Substance abuse/dependence (past 4 months) 12. Regular and frequent cannabis use (\> twice/week regularly) 13. Currently clinically significant suicidal ideation or Hamilton Depression Scale (HAM-D) score \>24 14. History or current psychosis or bipolar disorder 15. Pregnant or breastfeeding 16. Significant untreated insomnia (score \>3 on HAM-D insomnia items) 17. Currently taking psychostimulant medication or past nonresponse to modafinil 18. Has no alternative viable antiretroviral regimen after the current one 19. Left ventricular hypertrophy; mitral valve prolapse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue Severity Scale(FSS) Outcome | Measured at baseline and Weeks 4 | 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. |
| Role Function Scale | Measured at Baseline and Week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD4 Cell Count | Measured at baseline and Week 4 | 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. |
| HIV Viral Load | Measured at baseline and Week 4 | 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. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from community based organizations and healthcare clinics that provide services to persons with HIV, by placing flyers on bulletin boards and in waiting areas.
Pre-assignment details
A total of 114 patients were screened for eligibility, 25 had medical or psychiatric exclusion criteria, 7 were active substance users, 4 were taking stimulants, 3 were not clinically fatigued, 5 declined participation, and 70 were randomized. Of the 70, 64 completed the 4-week trial.
Participants by arm
| Arm | Count |
|---|---|
| Armodafinil Participants will receive armodafinil for 4 weeks. If responsive, participants will be offered 12 additional weeks of armodafinil. | 36 |
| Placebo Participants will receive a placebo pill for 4 weeks, then a 16-week course of armodafinil. | 34 |
| Total | 70 |
Baseline characteristics
| Characteristic | Placebo | Armodafinil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 36 Participants | 70 Participants |
| Age, Continuous | 46 years STANDARD_DEVIATION 8.2 | 46 years STANDARD_DEVIATION 8.7 | 46 years STANDARD_DEVIATION 8.4 |
| Region of Enrollment United States | 34 participants | 36 participants | 70 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 30 Participants | 31 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 36 | 0 / 34 |
| serious Total, serious adverse events | 0 / 36 | 0 / 34 |
Outcome results
Primary
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.
Time frame: Measured at baseline and Weeks 4
Population: Of the 70 patients randomized, 64 completed the 4-week trial. Data presented are for the 70, using the last data point carried forward (intention to treat).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Armodafinil | Fatigue Severity Scale(FSS) Outcome | Baseline FSS | 52.6 units on a scale | Standard Deviation 6.13 |
| Armodafinil | Fatigue Severity Scale(FSS) Outcome | Week 4 FSS | 25.8 units on a scale | Standard Deviation 14.23 |
| Placebo | Fatigue Severity Scale(FSS) Outcome | Baseline FSS | 53.1 units on a scale | Standard Deviation 6.87 |
| Placebo | Fatigue Severity Scale(FSS) Outcome | Week 4 FSS | 39.4 units on a scale | Standard Deviation 14.91 |
p-value: <0.001ANCOVA
Primary
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.
Time frame: Measured at Baseline and Week 4
Population: The week 4 outcome analyses are based on an intention to treat sample, which includes the 6 dropouts, using the last data point brought forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Armodafinil | Role Function Scale | Baseline Role Function Scale | 36.2 units on a scale | Standard Deviation 5.75 |
| Armodafinil | Role Function Scale | Week 4 Role Function Scale | 19.9 units on a scale | Standard Deviation 8.1 |
| Placebo | Role Function Scale | Baseline Role Function Scale | 37.8 units on a scale | Standard Deviation 7.81 |
| Placebo | Role Function Scale | Week 4 Role Function Scale | 28.3 units on a scale | Standard Deviation 10.19 |
Comparison: Repeated measure analysisp-value: 0.01ANCOVA
Secondary
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.
Time frame: Measured at baseline and Week 4
Population: Results were included for patients on whom baseline and week 4 labs were drawn.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Armodafinil | CD4 Cell Count | Baseline CD4 cell count | 502 Cells/mcL | Standard Deviation 202 |
| Armodafinil | CD4 Cell Count | Week 4 CD4 cell count | 503 Cells/mcL | Standard Deviation 224 |
| Placebo | CD4 Cell Count | Baseline CD4 cell count | 450 Cells/mcL | Standard Deviation 241 |
| Placebo | CD4 Cell Count | Week 4 CD4 cell count | 445 Cells/mcL | Standard Deviation 255 |
Comparison: Null hypothesis: CD4 levels for both the Armodafinil and Placebo groups will not change significantly between baseline and week 4.p-value: >=0.805Paired t-tests
Secondary
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.
Time frame: Measured at baseline and Week 4
Population: Results were included for patients on whom baseline and week 4 labs were drawn.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Armodafinil | HIV Viral Load | Baseline Log10 Viral Load | 2.17 Log10 copies/mL | Standard Deviation 0.81 |
| Armodafinil | HIV Viral Load | Week 4 Log10 Viral load | 2.15 Log10 copies/mL | Standard Deviation 0.87 |
| Placebo | HIV Viral Load | Baseline Log10 Viral Load | 2.39 Log10 copies/mL | Standard Deviation 1.13 |
| Placebo | HIV Viral Load | Week 4 Log10 Viral load | 2.24 Log10 copies/mL | Standard Deviation 1.07 |