Fatigue, HIV Infections
Conditions
Keywords
HIV, AIDS, Modafinil, Depression
Brief summary
This study will determine whether modafinil (Provigil®), a medication approved for the treatment of narcolepsy, 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. This study will determine if modafinil can reduce fatigue in HIV/AIDS patients. This study will last 12 weeks. Participants will be randomly assigned to receive either modafinil or placebo daily for 4 weeks. Participants who show an improvement in symptoms will receive modafinil for an additional 8 weeks. Participants who do not respond to modafinil will have the opportunity to receive other drug treatments. 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.
Interventions
DRUGModafinil
50 mg per day, increasing to 200 mg per day as clinically indicated
DRUGPlacebo
50 mg per day, increasing to 200 mg per day as clinically indicated
Sponsors
National Institute of Mental Health (NIMH)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, 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 \[O.I.\] 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 \[TSH\] 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 Rating Scale (HAM-D) \>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) | Measured at baseline and Week 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 to 63, with a higher value indicating greater impairment due to fatigue. |
| Role Function Scale Outcome | Measured at baseline and Week 4 | The Role Function Scale includes 10 items drawn from the Short Form 36-item Health 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 to 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 functioning. Blood was 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 RNA 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 presented in log10. 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 enrolled from January 2005 until December 2008.
Participants by arm
| Arm | Count |
|---|---|
| Modafinil Participants will take modafinil for 4 weeks. If responsive, participants will be offered 8 additional weeks of modafinil. | 62 |
| Placebo Participants will take placebo for 4 weeks, if not responsive, a 12-week course of modafinil will be offered. | 53 |
| Total | 115 |
Baseline characteristics
| Characteristic | Placebo | Total | Modafinil |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 113 Participants | 60 Participants |
| Age, Continuous | 45.74 years STANDARD_DEVIATION 8.57 | 45.84 years STANDARD_DEVIATION 8.96 | 45.94 years STANDARD_DEVIATION 9.35 |
| Region of Enrollment United States | 53 participants | 115 participants | 62 participants |
| Sex: Female, Male Female | 7 Participants | 15 Participants | 8 Participants |
| Sex: Female, Male Male | 46 Participants | 100 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 62 | 0 / 53 |
| serious Total, serious adverse events | 0 / 62 | 0 / 53 |
Outcome results
Primary
Fatigue Severity Scale (FSS)
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 to 63, with a higher value indicating greater impairment due to fatigue.
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 10 dropouts (2 on Modafinil and 8 on Placebo), using the last data point brought forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Modafinil | Fatigue Severity Scale (FSS) | Baseline FSS | 52 units on a scale | Standard Deviation 7 |
| Modafinil | Fatigue Severity Scale (FSS) | Week 4 FSS | 34 units on a scale | Standard Deviation 5 |
| Placebo | Fatigue Severity Scale (FSS) | Baseline FSS | 52 units on a scale | Standard Deviation 6 |
| Placebo | Fatigue Severity Scale (FSS) | Week 4 FSS | 43 units on a scale | Standard Deviation 13 |
p-value: <0.001ANCOVA
Primary
Role Function Scale Outcome
The Role Function Scale includes 10 items drawn from the Short Form 36-item Health 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 to 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 10 dropouts (2 on Modafinil and 8 on Placebo), using the last data point brought forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Modafinil | Role Function Scale Outcome | Baseline Role Function Scale | 39 units on a scale | Standard Deviation 7 |
| Modafinil | Role Function Scale Outcome | Week 4 Role Function Scale | 22 units on a scale | Standard Deviation 9 |
| Placebo | Role Function Scale Outcome | Baseline Role Function Scale | 36 units on a scale | Standard Deviation 6 |
| Placebo | Role Function Scale Outcome | Week 4 Role Function Scale | 27 units on a scale | Standard Deviation 11 |
p-value: <0.001ANCOVA
Secondary
CD4 Cell Count
CD4 cell count is a laboratory marker providing an indication of immune functioning. Blood was 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 |
|---|---|---|---|---|
| Modafinil | CD4 Cell Count | Baseline CD4 cell count | 481 Cells/mcL | Standard Deviation 249 |
| Modafinil | CD4 Cell Count | Week 4 CD4 cell count | 466 Cells/mcL | Standard Deviation 244 |
| Placebo | CD4 Cell Count | Baseline CD4 cell count | 459 Cells/mcL | Standard Deviation 257 |
| Placebo | CD4 Cell Count | Week 4 CD4 cell count | 482 Cells/mcL | Standard Deviation 240 |
Comparison: Week 4 CD4 cell countp-value: 0.15ANOVA
Secondary
HIV RNA 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 presented in log10. 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 |
|---|---|---|---|---|
| Modafinil | HIV RNA Viral Load | Baseline Log10 Viral Load | 2.53 Log10 copies/mL | Standard Deviation 1.2 |
| Modafinil | HIV RNA Viral Load | Week 4 Log10 Viral load | 2.31 Log10 copies/mL | Standard Deviation 1 |
| Placebo | HIV RNA Viral Load | Baseline Log10 Viral Load | 2.41 Log10 copies/mL | Standard Deviation 1.2 |
| Placebo | HIV RNA Viral Load | Week 4 Log10 Viral load | 2.30 Log10 copies/mL | Standard Deviation 1.1 |
p-value: 0.459ANOVA