WHATIF: Clinical Trial to Reduce Drinking in Women With HIV

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT01625091
• Collaborator: Florida International University (Other), University of Miami (Other), Rush University (Other), National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 194
• Locations: 2
• Arms: 2
• Actual Duration (Months): 43
• Patients Per Site: 97
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate whether an intervention that involves the medication naltrexone, will reduce drinking and improve health outcomes in women with HIV infection and hazardous drinking. Our central hypotheses are that, compared to women who receive placebo (sugar pill containing no medicine), women who receive naltrexone will have decreased rates of hazardous drinking, improved HIV medication adherence, less rapid disease progression, and reduced sexual risk behavior. The study design will involve 240 HIV-infected women with hazardous drinking, who will be recruited from HIV clinics, neighborhoods and referrals in Miami, Florida.

Eligible women will receive either a daily pill containing naltrexone (50mg) or an identical-appearing placebo for four months. All participants will receive encouragement and feedback related to their drinking regardless of medication assignment. The study participants will be assessed at two, four and seven months after enrollment. The proposed work is innovative because pharmacologic treatment for alcohol has not been evaluated in HIV-infected women. If our hypotheses are confirmed, the study findings would transform the approach to hazardous drinking within clinics serving HIV-infected women.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection	Drug: Naltrexone; Drug: Placebo	Phase 3

Detailed Description

The primary objective of this study is to evaluate the acceptability and effectiveness of a treatment program for hazardous drinking, delivered within HIV-clinic outpatient settings, that involves oral naltrexone. The central hypothesis is that women participating in the treatment program will have decreased rates of hazardous drinking and improved clinical and behavioral health outcomes that are associated with hazardous drinking. The investigators have formulated this hypotheses based on the existing literature, the preliminary data and the clinical experience. The investigators theorize that women who receive an alcohol treatment intervention will be less likely to have "at risk" drinking behavior 6-months after enrollment, compared to women who received similar assessments but no formal treatment intervention. The investigators hypothesize that 4-months after enrollment, women who receive an alcohol treatment intervention will have improved adherence to HIV antiretroviral therapy, improved CD4 cell counts, reduced HIV viral load, and reduced risky sexual behavior, compared to women who receive similar assessments but no formal intervention.

The investigators will recruit 240 women from one site in Miami, Florida. Of those 240 women 120 will receive naltrexone and the others will receive placebo. Study participants will take the medication for 4 months but the investigators will follow them for 7 months. At baseline, 2 months, 4 months and 7 months, the investigators will administer study questionnaires and assess their liver enzymes, CD4 count and viral load. The investigators will also follow them up at months 1 and 3 to reinforce the medication intake and to assess for any possible side effects.

New treatment options are available, but their impact on hazardous drinking has not yet been evaluated among HIV-infected women, many of whom are poor, minorities, or who have associated mental health or substance abuse problems. Delivery of therapeutic interventions must be improved in order to reduce hazardous drinking in women with HIV/AIDS. The proposed research is significant because the therapy will be offered within HIV clinic settings and will potentially improve the health of a population that is significantly undertreated. In addition to determining the effectiveness of an alcohol treatment intervention, the investigators will also identify key barriers and facilitators associated with adherence to pharmacologic treatment for alcohol in women with hazardous drinking. The findings will directly affect the type and quality of care for hazardous drinking in this subset of HIV-infected individuals and will inform both primary and secondary prevention efforts.

Study Design

• Study Type: Interventional
• Actual Enrollment: 194 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pharmacotherapy for Alcohol Consumption in HIV Infected Women: Randomized Trial
• Actual Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: naltrexone The investigators will administer Naltrexone to women with hazardous drinking and assess the study outcomes.	Drug: Naltrexone; The study involves taking the drug naltrexone for up to 4 months. This will be given in a single pill each day for 4 months.
Placebo Comparator: placebo pill The investigators will administer an inert placebo that looks similar to Naltrexone, to women with hazardous drinking and assess the study outcomes.	Drug: Placebo; Placebo is an inert pill that looks the same as naltrexone. The placebo will be taken once each day for up to 4 months.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Quit Hazardous Drinking [Month 4]

   The primary statistical outcome for the trial is alcohol consumption at month 4 when the drug is stopped. This main outcome is a categorical variable of either quit hazardous drinking (defined as ≤7 drinks per week and <4 drinks on any single day in the past 30 days), or did not quit (drinking exceeds the hazardous amount) .

Secondary Outcome Measures

1. Number of Binge Drinking Days [Month 4]

   In the past 30 days, total number of days with binge drinking which was defined as consuming ≥4 drinks on a single day (measured by Timeline Follow Back).

2. Drinking Problems (SIP-2R Score) [4 months]

   The Short Inventory of Problems (SIP-2R) seeks to measure the consequences of drinking in participants through questions related to guilt, reliability etc. The SIP-2R has 15 items asking how often the event happened during the past 3 months. Each item has a score from 0-3 (0=Never, 1=once or a few times, 2=once or twice a week, 3=daily or almost daily). The 15 questions from the SIP-2R are summed to create a total range of scores from 0-45.

3. Craving for Alcohol [4 months]

   Self-reported scale of alcohol craving ranging from 0 (no craving) to 10 (strongest craving)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria: (must meet all of following):

• Hazardous drinking, on average, during the preceding 4 weeks. Defined as binge drinking (4 or more drinks per occasion at least twice monthly) and/or high total weekly consumption (>7 drinks per week).

• Age 18 or over

• Female

• HIV infection (documented by medical record blood test result or testing done for this study)

• Able to understand and comply with study procedures and to provide written consent.

Exclusion criteria: (cannot have any of the following):

• Contraindications to treatment with naltrexone

• Current physiologic opiate dependence

• Current daily prescription opioid medications

• Positive urine drug test for opioids

• Allergic to naltrexone

• Significantly abnormal baseline liver enzymes (AST or ALT >=5 times upper normal), evidence of acute hepatitis, or receiving hemodialysis for renal failure

• Currently pregnant

• Currently taking an alcohol treatment medication (disulfiram, topiramate, naltrexone, acamprosate).

• Currently unable to provide mailing address or reliable contact information, or has plans to move from area within next 7 months

• Unable to communicate in English or Spanish

• Research coordinator assessment that participant cannot comprehend the study or consent procedures (e.g. participant appears to be intoxicated, answers questions in a non-sensible manner)

• Has current prognosis of less than one year to live (e.g. in Hospice, has metastatic cancer)

• Currently taking antiviral treatment for hepatitis C infection (interferon or ribavirin)

• Has other unique health condition, not specifically listed, that should exclude the participant after discussion with Dr. Cook, Dr. Espinoza, and perhaps also the participant's primary HIV physician (for example an unexpected abnormal laboratory result turns up on the baseline screening metabolic panel).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Coral Gables	Florida	United States	33124
2	Florida International University	Miami	Florida	United States	33199

Sponsors and Collaborators

• University of Florida
• Florida International University
• University of Miami
• Rush University
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Robert L Cook, MD, MPH, University of Florida

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT01625091
• Other Study ID Numbers: 86-2012-N; U01AA020797-01
• First Posted: Jun 21, 2012
• Last Update Posted: Jul 10, 2018
• Last Verified: Jun 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Florida: HIV; women; drinking; Naltrexone
• Additional relevant MeSH terms: HIV Infections; Naltrexone

Study Results

Participant Flow

Arm/Group Title	Naltrexone	Placebo
Arm/Group Description	The participants took the drug naltrexone one single pill (50mg) each day for up to 4 months and then received final assessment at 7-months.	The participants took an inert placebo one single pill each day for up to 4-months and then received final assessment at 7-months. Placebo is an inert pill that looks the same as naltrexone.
Period Title: Intervention
STARTED	96	98
2 Months	90	93
4 Months	85	87
COMPLETED	85	87
NOT COMPLETED	11	11
Period Title: Intervention
STARTED	85	87
7 Months	81	85
COMPLETED	81	85
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Naltrexone	Placebo	Total
Arm/Group Description	The participants took the drug naltrexone one single pill (50mg) each day for up to 4 months and then received final assessment at 7-months.	The participants took an inert placebo one single pill each day for up to 4-months and then received final assessment at 7-months. Placebo is an inert pill that looks the same as naltrexone.	Total of all reporting groups
Overall Participants	96	98	194
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.7 (8.5)	48.9 (8.9)	48.3 (8.7)
Age, Customized (Count of Participants)
18-39	16 16.7%	13 13.3%	29 14.9%
40-49	35 36.5%	32 32.7%	67 34.5%
50-59	37 38.5%	43 43.9%	80 41.2%
≥60	8 8.3%	10 10.2%	18 9.3%
Sex: Female, Male (Count of Participants)
Female	96 100%	98 100%	194 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Hispanic	11 11.5%	11 11.2%	22 11.3%
Not Hispanic, White	3 3.1%	5 5.1%	8 4.1%
Not Hispanic, Black	81 84.4%	80 81.6%	161 83%
Not Hispanic, Other	1 1%	2 2%	3 1.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Quit Hazardous Drinking
Description	The primary statistical outcome for the trial is alcohol consumption at month 4 when the drug is stopped. This main outcome is a categorical variable of either quit hazardous drinking (defined as ≤7 drinks per week and <4 drinks on any single day in the past 30 days), or did not quit (drinking exceeds the hazardous amount) .
Time Frame	Month 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naltrexone	Placebo
Arm/Group Description	The participants took the drug naltrexone one single pill (50mg) each day for up to 4 months and then received final assessment at 7-months.	The participants took an inert placebo one single pill each day for up to 4-months and then received final assessment at 7-months. Placebo is an inert pill that looks the same as naltrexone.
Measure Participants	85	87
Count of Participants [Participants]	44 45.8%	39 39.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naltrexone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Number of Binge Drinking Days
Description	In the past 30 days, total number of days with binge drinking which was defined as consuming ≥4 drinks on a single day (measured by Timeline Follow Back).
Time Frame	Month 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naltrexone	Placebo
Arm/Group Description	The participants took the drug naltrexone one single pill (50mg) each day for up to 4 months and then received final assessment at 7-months.	The participants took an inert placebo one single pill each day for up to 4-months and then received final assessment at 7-months. Placebo is an inert pill that looks the same as naltrexone.
Measure Participants	85	87
Median (95% Confidence Interval) [Days]	0	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naltrexone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Drinking Problems (SIP-2R Score)
Description	The Short Inventory of Problems (SIP-2R) seeks to measure the consequences of drinking in participants through questions related to guilt, reliability etc. The SIP-2R has 15 items asking how often the event happened during the past 3 months. Each item has a score from 0-3 (0=Never, 1=once or a few times, 2=once or twice a week, 3=daily or almost daily). The 15 questions from the SIP-2R are summed to create a total range of scores from 0-45.
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naltrexone	Placebo
Arm/Group Description	The participants took the drug naltrexone one single pill (50mg) each day for up to 4 months and then received final assessment at 7-months.	The participants took an inert placebo one single pill each day for up to 4-months and then received final assessment at 7-months. Placebo is an inert pill that looks the same as naltrexone.
Measure Participants	85	87
Mean (Standard Deviation) [units on a scale]	7.2 (9.9)	6.7 (8.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naltrexone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Craving for Alcohol
Description	Self-reported scale of alcohol craving ranging from 0 (no craving) to 10 (strongest craving)
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naltrexone	Placebo
Arm/Group Description	The participants took the drug naltrexone one single pill (50mg) each day for up to 4 months and then received final assessment at 7-months.	The participants took an inert placebo one single pill each day for up to 4-months and then received final assessment at 7-months. Placebo is an inert pill that looks the same as naltrexone.
Measure Participants	85	87
Mean (Standard Deviation) [units on a scale]	3.3 (3.4)	3.2 (2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naltrexone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	7 months
Arm/Group Title	Naltrexone		Placebo
Arm/Group Description	The participants took the drug naltrexone one single pill (50mg) each day for up to 4 months and then received final assessment at 7-months.		The participants took an inert placebo one single pill each day for up to 4-months and then received final assessment at 7-months. Placebo is an inert pill that looks the same as naltrexone.
All Cause Mortality
	Naltrexone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/96 (1%)		2/98 (2%)
Serious Adverse Events
	Naltrexone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/96 (10.4%)		6/98 (6.1%)
General disorders
Inpatient hospitalization	10/96 (10.4%)	10	6/98 (6.1%)	6
Other (Not Including Serious) Adverse Events
	Naltrexone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/96 (80.2%)		74/98 (75.5%)
Gastrointestinal disorders
Nausea	35/96 (36.5%)		29/98 (29.6%)
Diarrhea	23/96 (24%)		27/98 (27.6%)
Vomiting	22/96 (22.9%)		8/98 (8.2%)
General disorders
Fatigue	28/96 (29.2%)		18/98 (18.4%)
Decreased appetite	21/96 (21.9%)		23/98 (23.5%)
Sleepiness	24/96 (25%)		19/98 (19.4%)
Dizziness	23/96 (24%)		14/98 (14.3%)
Abdominal pain	20/96 (20.8%)		13/98 (13.3%)
Insomnia	15/96 (15.6%)		14/98 (14.3%)
Nervous system disorders
Headache	28/96 (29.2%)		19/98 (19.4%)
Psychiatric disorders
Depression	27/96 (28.1%)		16/98 (16.3%)
Nervousness/Anxiety	16/96 (16.7%)		18/98 (18.4%)
Skin and subcutaneous tissue disorders
Itchiness	15/96 (15.6%)		21/98 (21.4%)

Limitations/Caveats

[Not Specified]

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.