Mechanisms of Lipodystrophy in HIV-Infected Pateints

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00457665
• Collaborator: Bristol-Myers Squibb (Industry), GlaxoSmithKline (Industry)
• Enrollment: 56
• Location: 1
• Arms: 2
• Duration (Months): 152
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The metabolic and molecular basis of lipodystrophy syndrome in HIV-infected patients is not known. Whether besides protease inhibitors, other antiretroviral drugs, HIV infection and reduction in viral load contribute to the development of lipodystrophy syndrome is not clear.

The project therefore has the following aims: 1) to characterize metabolic abnormalities and changes in body fat distribution, 2) to develop objective criteria for defining the syndrome and to ascertain prognostic indicators and 3) to elucidate the molecular basis of the lipodystrophy syndrome in HIV-infected patients.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Nelfinavir; Drug: Efavirenz	Phase 4

Detailed Description

A 2-year long prospective, randomized, double blind, placebo-controlled study in 200 asymptomatic HIV (+) patients to compare two equally effective antiretroviral regimens, one with and the other without a protease inhibiotor. We will study body fat distribution by anthropometry and magnetic resonance imaging and will measure insulin sensitivity (in a subset of patients), plasma lipoproteins, glucose tolerance and other metabolic variables. We will study expression of an array of adipocyte specific proteins/transcription factors involved in adipocyte differentiation, insulin action and lipoprotein metabolism in fat biopsy samples obtained before and after institution of therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Mecahnisms of Lipodystrophy in HIV-Infected Patients
• Study Start Date: Feb 1, 2002
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nelfinavir (Viracept)	Drug: Nelfinavir; Other Names: Viracept
Active Comparator: Efavirenz (Sustiva)	Drug: Efavirenz

Outcome Measures

Primary Outcome Measures

1. Effect of Drug Regimens on Serum Triglycerides. [12 and 24 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV Positive

• No previous antiviral therapy

• 18 to 70 years of age

Exclusion Criteria:

• Patients with opportunistic infections or AIDS.

• Active intravenous drug users.

• Patients on corticosteroids, androgens, lipid-lowering drugs, anti-fungal medications, dehydroepiandrosterone, oxandrolone, megace.

• Patients with diabetes mellitus.

• Patients with moderate to heavy alcohol consumption ( greater than 15 drinks per week).

• Pregnant or premenopausal women, unless surgically sterilized or highly unlikely to conceive (defined as women taking oral contraceptives, using barrier protection during intercourse or with a copper intrauterine device in place for > 3 months without complaints and a negative serum or urine pregnancy test within 30 days of study entry).

• Acute or chronic liver diseases; elevations of liver transaminases by more than two and one half times above the upper limits of normal ( SGOT > 105 U/L, SGPT > 120 U/L, ) or a total bilirubin of > 1.5mg/dL.

• Anemia (hematocrit <32%).

• Abnormal thyroid function tests.

• Weight loss >10% from baseline in the past year.

• Recent (within the past year), history of suicide attempt.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390

Sponsors and Collaborators

• University of Texas Southwestern Medical Center
• Bristol-Myers Squibb
• GlaxoSmithKline

Investigators

• Principal Investigator: Abhimanyu Garg, M.D., University of Texas Southwestern Medical Center Dallas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00457665
• Other Study ID Numbers: R01-56583
• First Posted: Apr 6, 2007
• Last Update Posted: Jul 18, 2019
• Last Verified: May 1, 2019

• Keywords provided by , ,: HIV; Lipodystrophy; Treatment Experienced
• Additional relevant MeSH terms: Lipodystrophy; Efavirenz; Nelfinavir

Study Results

Participant Flow

Arm/Group Title	Nelfinavir	Efavirenz
Arm/Group Description	Randomized to receive Nelfinavir inclusive HAART	Randomized to receive Efavirenz inclusive HAART
Period Title: 12 Months
STARTED	28	28
COMPLETED	20	19
NOT COMPLETED	8	9
Period Title: 12 Months
STARTED	20	19
COMPLETED	15	11
NOT COMPLETED	5	8

Baseline Characteristics

Arm/Group Title	Nelfinavir	Efavirenz	Total
Arm/Group Description	Randomized to receive Nelfinavir inclusive HAART	Randomized to receive Efavirenz inclusive HAART	Total of all reporting groups
Overall Participants	28	28	56
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	28 100%	28 100%	56 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 17.9%	4 14.3%	9 16.1%
Male	23 82.1%	24 85.7%	47 83.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 17.9%	5 17.9%	10 17.9%
White	14 50%	19 67.9%	33 58.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	9 32.1%	4 14.3%	13 23.2%
Weight (kgs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kgs]	75.4 (11)	75 (13.8)	75.18 (12.3)
Body Mass Index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	25.2 (3.8)	24.8 (5)	24.9 (4.3)
CD4 count (per cubic mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [per cubic mm]	312 (210)	301 (158)	307 (185)
HIV Viral load (copies per mL) [Median (Full Range) ]
Median (Full Range) [copies per mL]	82000	103000	97900
Fasting plasma glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	92.5 (9.0)	90.3 (5.6)	91.4 (7.4)
Triglycerides (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	129 (83.8)	133.5 (81.4)	131.24 (82)

Outcome Measures

1. Primary Outcome

Title	Effect of Drug Regimens on Serum Triglycerides.
Time Frame	12 and 24 months

Outcome Measure Data

Analysis Population Description

Some subjects dropped before 1 year and some dropped between 1-2 years.

Arm/Group Title	Nelfinavir (Viracept)	Efavirenz (Sustiva)
Arm/Group Description	Assigned to Nelfinavir	Assigned to Efavirenz
Measure Participants	20	20
At 12 months	228.0 (119.0)	230.4 (157.3)
At 24 months	293.4 (350.6)	290.0 (276.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nelfinavir (Viracept), Efavirenz (Sustiva)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	24 months
Arm/Group Title	Nelfinavir		Efavirenz
Arm/Group Description	These participants were randomized to receive Nelfinavir		These participants were randomized to receive Efavirenz
All Cause Mortality
	Nelfinavir		Efavirenz
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/28 (0%)
Serious Adverse Events
	Nelfinavir		Efavirenz
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/28 (3.6%)		2/28 (7.1%)
Gastrointestinal disorders
Gastritis	1/28 (3.6%)	1	0/28 (0%)	0
Vomiting and diarrhea	0/28 (0%)	0	1/28 (3.6%)	1
Skin and subcutaneous tissue disorders
Spider bite	0/28 (0%)	0	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	Nelfinavir		Efavirenz
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/28 (71.4%)		20/28 (71.4%)
Gastrointestinal disorders
Diarrhea	13/28 (46.4%)		1/28 (3.6%)
Hepatobiliary disorders
Abnormal liver function tests	1/28 (3.6%)	1	10/28 (35.7%)	10
Nervous system disorders
Peripheral neuropathy	6/28 (21.4%)	6	10/28 (35.7%)	10
Psychiatric disorders
Disturbing dreams	2/28 (7.1%)		9/28 (32.1%)
Skin and subcutaneous tissue disorders
Skin rash	1/28 (3.6%)	1	5/28 (17.9%)	5

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.