Randomized, Placebo-Controlled Study of Leptin for the Treatment of HIV Lipodystrophy and Metabolic Syndrome

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00140244
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Amgen (Industry)
• Enrollment: 7
• Location: 1
• Arms: 2
• Duration (Months): 114
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to examine whether replacing leptin to normal levels can reverse the changes in fat distribution, lipid profile, and other metabolic problems associated with highly active antiretroviral therapy (HAART)-induced lipodystrophy and metabolic syndrome in HIV patients.

Condition or Disease	Intervention/Treatment	Phase
HAART-induced Lipodystrophy and Metabolic Syndrome	Drug: r-metHuLeptin; Drug: Placebo	Phase 2

Detailed Description

Exposure to HIV medications has been associated with metabolic changes including generalized fat depletion (lipoatrophy), high triglyceride levels, and in some patients, high sugar levels or diabetes. This syndrome is associated with a deficiency of leptin, a hormone produced by fat cells. Recent studies involving leptin administration to patients with congenital lipoatrophy have shown dramatic improvements in metabolic parameters such as insulin resistance and hyperlipidemia. Leptin administration to patients with HAART-induced lipoatrophy may also lead to significant improvements in the metabolic abnormalities found in these HIV+ patients. The aims of this study are to examine the effect of leptin administration on insulin resistance and other parameters of the metabolic syndrome in HIV patients with HAART-induced lipoatrophy.

Comparison: Leptin-treated group to placebo-treated group

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Role of Leptin in Highly Active Antiretroviral Therapy (HAART)-Induced Lipodystrophy and Metabolic Syndrome in HAART-Treated HIV Patients
• Study Start Date: Dec 1, 2001
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: r-MetHuLeptin r-MetHuLeptin SubQ once daily	Drug: r-metHuLeptin
Placebo Comparator: Placebo SubQ once daily	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Serum Lipid Levels [At the end of each two month intervention]

Secondary Outcome Measures

1. Insulin Resistance (as Assessed by HOMA-IR) [At the end of each two month intervention]

2. Glycemia (as Assessed by Fasting Glucose) [At the end of each two month intervention]

3. Low Density Lipoprotein (LDL) Cholesterol Levels [At the end of each two month intervention]

4. Free Fatty Acid (FFA) Levels [At the end of each two month intervention]

5. Blood Pressure [At the end of each two month intervention]

   percent change in mean blood pressure

6. Fibrinogen [At the end of each two month intervention]

   Fibrinogen

7. Insulin Levels [At the end of each two month intervention]

8. Lean Body Mass [At the end of each two month intervention]

   lean body mass

9. Viral Load [At the end of each two month intervention]

10. CD4+ Lymphocytes [At the end of each two month intervention]

11. Interleukin-6 (IL-6) Levels [At the end of each two month intervention]

12. Hepatic Fat Content [At the end of each two month intervention]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At least 18 years old

• Documented HIV infection

• Exposed to at least 6 months of cumulative highly active antiretroviral medications for HIV

• Developed fat depletion after starting HIV medications

• Low leptin level in the blood

• Fasting triglyceride level > 300 mg/dl

Exclusion Criteria:

• Active infectious diseases, except HIV

• Diabetes prior to starting HIV medications

• Alcohol or drug abuse

• Triglyceride level > 1000 mg/dl

• Significant kidney, liver, or thyroid dysfunction

• Cancer or lymphoma

• Pregnancy or planning to become pregnant during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Amgen

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for more information about the Mantzoros Research Group.
• Click here for more information about Beth Israel Deaconess Medical Center.

Publications

None provided.

• Responsible Party: Christos Mantzoros, Professor of Medicine, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT00140244
• Other Study ID Numbers: 2001P000484; R01DK058785
• First Posted: Sep 1, 2005
• Last Update Posted: May 11, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Christos Mantzoros, Professor of Medicine, Beth Israel Deaconess Medical Center: leptin; lipodystrophy; insulin resistance; hyperlipidemia; metabolic syndrome
• Additional relevant MeSH terms: Lipodystrophy; Metabolic Syndrome; Syndrome

Study Results

Participant Flow

Arm/Group Title	r-MetHuLeptin First, Then Placebo	Placebo First, Then r-metHuLeptin
Arm/Group Description	r-MetHuLeptin subcutaneously once daily first, then Placebo both at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Subcutaneously once daily Placebo first, then r-metHuLeptin both at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Period Title: Intervention 1
STARTED	3	4
COMPLETED	3	4
NOT COMPLETED	0	0
Period Title: Intervention 1
STARTED	3	4
COMPLETED	3	4
NOT COMPLETED	0	0
Period Title: Intervention 1
STARTED	3	4
COMPLETED	3	2
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	r-MetHuLeptin SubQ once daily r-metHuLeptin/placebo then placebo/r-metHuLeptin
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.8 (2)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	7 100%
Region of Enrollment (participants) [Number]
United States	7 100%
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	22.2 (0.83)
Fasting leptin concentration (ng/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ml]	1.34 (0.2)
triglycerides (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	530 (53.8)
insulin (micro international units(μIU)/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [micro international units(μIU)/ml]	11.5 (2.7)
glucose (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	81.1 (6.7)
hemoglobin A1c (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	5.1 (0.3)
CD4 count (cells/μl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/μl]	454 (94)
HIV viral load (copies/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [copies/ml]	24524 (13693)

Outcome Measures

1. Primary Outcome

Title	Serum Lipid Levels
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
total cholesterol	228.8 (13.3)	219.7 (13.1)
low density lipoprotein cholesterol	113.0 (12.7)	105.7 (3.33)
triglycerides	409.0 (88.8)	520.5 (91.1)
high density lipoprotein cholesterols	35 (2.23)	29.96 (2.25)
Free fatty acids	0.45 (0.07)	0.61 (0.09)

2. Secondary Outcome

Title	Insulin Resistance (as Assessed by HOMA-IR)
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-metHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [units on a scale]	2.52 (0.91)	4.56 (1.43)

3. Secondary Outcome

Title	Glycemia (as Assessed by Fasting Glucose)
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [mg/dl]	91 (2.28)	95.6 (2.8)

4. Secondary Outcome

Title	Low Density Lipoprotein (LDL) Cholesterol Levels
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [mg/dl]	113 (12.7)	105.7 (3.33)

5. Secondary Outcome

Title	Free Fatty Acid (FFA) Levels
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [mEq/liter]	0.45 (0.07)	0.61 (0.09)

6. Secondary Outcome

Title	Blood Pressure
Description	percent change in mean blood pressure
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Least Squares Mean (Standard Error) [percentage change of mean blood pressure]	3.2 (5.7)	-6.7 (6.4)

7. Secondary Outcome

Title	Fibrinogen
Description	Fibrinogen
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [mg/dL]	252.2 (16.3)	294.4 (14.58)

8. Secondary Outcome

Title	Insulin Levels
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [mcIU/ml]	11.6 (4.46)	20.3 (7.04)

9. Secondary Outcome

Title	Lean Body Mass
Description	lean body mass
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [kg]	58.6 (4.41)	61.6 (4.26)

10. Secondary Outcome

Title	Viral Load
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [copies/ml]	11345 (10596)	12367 (11861)

11. Secondary Outcome

Title	CD4+ Lymphocytes
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [cells/mcl]	556.6 (135)	637.2 (158.4)

12. Secondary Outcome

Title	Interleukin-6 (IL-6) Levels
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [pg/ml]	1.65 (0.38)	2.14 (0.53)

13. Secondary Outcome

Title	Hepatic Fat Content
Time Frame	At the end of each two month intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	r-MetHuLeptin	Placebo
Arm/Group Description	r-MetHuLeptin at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.	Placebo at a dose of 0.04 mg/kg/day divided into two equal doses, which were self-administered by sc injection at 0800 and 2000 h daily for 2 months.
Measure Participants	5	7
Mean (Standard Error) [percentage of liver volume]	4.02 (3.15)	4.01 (2.65)

Adverse Events

Arm/Group Title	r-MetHuLeptin		Placebo
Arm/Group Description
All Cause Mortality
	r-MetHuLeptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	r-MetHuLeptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	r-MetHuLeptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.