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

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00118378
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 115
• Location: 1
• Arms: 2
• Duration (Months): 71
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Fatigue	Drug: Modafinil; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 115 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Modafinil Treatment for Fatigue in HIV+ Patients
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Modafinil Participants will take modafinil for 4 weeks.	Drug: Modafinil; 50 mg per day, increasing to 200 mg per day as clinically indicated; Other Names: Provigil
Placebo Comparator: Placebo Participants will take placebo for 4 weeks.	Drug: Placebo; 50 mg per day, increasing to 200 mg per day as clinically indicated; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Judith G. Rabkin, PhD, MPH, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for a related study currently recruiting participants.

Publications

• Rabkin JG, McElhiney MC, Rabkin R, Ferrando SJ. Modafinil treatment for fatigue in HIV+ patients: a pilot study. J Clin Psychiatry. 2004 Dec;65(12):1688-95.

• Responsible Party: New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT00118378
• Other Study ID Numbers: #4839; R01MH072383-01; DAHBR 9A-ASNM
• First Posted: Jul 11, 2005
• Last Update Posted: May 10, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by New York State Psychiatric Institute: HIV; AIDS; Modafinil; Depression
• Additional relevant MeSH terms: Fatigue; Modafinil

Study Results

Participant Flow

Recruitment Details	Patients were enrolled from January 2005 until December 2008.

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Participants will take modafinil for 4 weeks. If responsive, participants will be offered 8 additional weeks of modafinil.	Participants will take placebo for 4 weeks, if not responsive, a 12-week course of modafinil will be offered.
Period Title: Overall Study
STARTED	62	53
COMPLETED	60	45
NOT COMPLETED	2	8

Baseline Characteristics

Arm/Group Title	Modafinil	Placebo	Total
Arm/Group Description	Participants will take modafinil for 4 weeks. If responsive, participants will be offered 8 additional weeks of modafinil.	Participants will take placebo for 4 weeks, if not responsive, a 12-week course of modafinil will be offered.	Total of all reporting groups
Overall Participants	62	53	115
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	60 96.8%	53 100%	113 98.3%
>=65 years	2 3.2%	0 0%	2 1.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.94 (9.35)	45.74 (8.57)	45.84 (8.96)
Sex: Female, Male (Count of Participants)
Female	8 12.9%	7 13.2%	15 13%
Male	54 87.1%	46 86.8%	100 87%
Region of Enrollment (participants) [Number]
United States	62 100%	53 100%	115 100%

Outcome Measures

1. Primary Outcome

Title	Fatigue Severity Scale (FSS)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Modafinil	Placebo
Arm/Group Description	Participants randomized to modafinil for 4 weeks. If responsive, participants will be offered 8 additional weeks of modafinil.	Participants randomized to placebo for 4 weeks, if not responsive, a 12-week course of modafinil will be offered.
Measure Participants	62	53
Baseline FSS	52 (7)	52 (6)
Week 4 FSS	34 (5)	43 (13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modafinil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Role Function Scale Outcome
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Modafinil	Placebo
Arm/Group Description	Participants randomized to modafinil for 4 weeks. If responsive, participants will be offered 8 additional weeks of modafinil.	Participants randomized to placebo for 4 weeks, if not responsive, a 12-week course of modafinil will be offered.
Measure Participants	62	53
Baseline Role Function Scale	39 (7)	36 (6)
Week 4 Role Function Scale	22 (9)	27 (11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modafinil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	CD4 Cell Count
Description	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

Outcome Measure Data

Analysis Population Description

Results were included for patients on whom baseline and week 4 labs were drawn.

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Participants randomized to modafinil for 4 weeks.	Participants randomized to placebo for 4 weeks.
Measure Participants	58	44
Baseline CD4 cell count	481 (249)	459 (257)
Week 4 CD4 cell count	466 (244)	482 (240)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modafinil, Placebo
	Comments	Week 4 CD4 cell count
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.150
	Comments
	Method	ANOVA
	Comments

4. Secondary Outcome

Title	HIV RNA Viral Load
Description	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

Outcome Measure Data

Analysis Population Description

Results were included for patients on whom baseline and week 4 labs were drawn.

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Participants randomized to modafinil for 4 weeks.	Participants randomized to placebo for 4 weeks.
Measure Participants	58	44
Baseline Log10 Viral Load	2.53 (1.2)	2.41 (1.2)
Week 4 Log10 Viral load	2.31 (1.0)	2.30 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modafinil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.459
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	Weeks 1-4 during the double-blind phase of the study.
Arm/Group Title	Modafinil		Placebo
Arm/Group Description	Participants will take modafinil for 4 weeks. If responsive, participants will be offered 8 additional weeks of modafinil.		Participants will take placebo for 4 weeks, if not responsive, a 12-week course of modafinil will be offered.
All Cause Mortality
	Modafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Modafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/53 (0%)
Other (Not Including Serious) Adverse Events
	Modafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/53 (0%)

Limitations/Caveats

This study was conducted at a single site in an urban setting where most patients have good access to medical care. Women were under-represented despite outreach efforts.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.