Trial Outcomes & Findings for Leptin for Abnormal Lipid Kinetics in HIV Lipodystrophy Syndrome (NCT NCT01511016)

Results Overview

Rate of total lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

17 participants

Primary outcome timeframe

4 months after treatment

Results posted on

2016-01-27

Participant Flow

HIV-positive subjects meeting the entry criteria were recruited from March, 2003 until November, 2010 from the clinics of Harris County Hospital District, and Legacy Community Health Center, Houston.

If a potential study subject was already taking a lipid lowering medication at the time of screening but was otherwise eligible for the study, he/she was invited to stop the medication for 6 weeks, at the end of which the fasting triglyceride level was re-measured to gauge eligibility.

Participant milestones

Participant milestones
Measure	Placebo Injection Each subject will receive placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Placebo : Placebo will administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.	Human Recombinant Leptin (Metreleptin) Each subject will receive 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Human recombinant leptin ("metreleptin") : Metreleptin will be administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
Overall Study STARTED	8	9
Overall Study COMPLETED	6	7
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Leptin for Abnormal Lipid Kinetics in HIV Lipodystrophy Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Injection n=8 Participants Each subject will receive placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Placebo : Placebo will administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.	Human Recombinant Leptin (Metreleptin) n=9 Participants Each subject will receive 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Human recombinant leptin ("metreleptin") : Metreleptin will be administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.	Total n=17 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	49.1 years STANDARD_DEVIATION 6.8 • n=5 Participants	44.9 years STANDARD_DEVIATION 7.8 • n=7 Participants	46.9 years STANDARD_DEVIATION 7.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 months after treatment

Population: Subjects in each group were analyzed and compared after 4 months of treatment.

Rate of total lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate

Outcome measures

Outcome measures
Measure	Placebo Injection n=8 Participants Each subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Placebo : Placebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.	Human Recombinant Leptin (Metreleptin) n=9 Participants Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Human recombinant leptin ("metreleptin") : Metreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
Rate of Total Lipolysis	0.649 mmol FFA/kg/h Standard Error 0.073	0.767 mmol FFA/kg/h Standard Error 0.137

PRIMARY outcome

Timeframe: 4 months after treatment

Population: Subjects in each group were analyzed and compared after 4 months of treatment

Rate of net lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate

Outcome measures

Outcome measures
Measure	Placebo Injection n=8 Participants Each subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Placebo : Placebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.	Human Recombinant Leptin (Metreleptin) n=9 Participants Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Human recombinant leptin ("metreleptin") : Metreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
Rate of Net Lipolysis	0.386 mmol FFA/kg/h Standard Error .074	0.508 mmol FFA/kg/h Standard Error .106

SECONDARY outcome

Timeframe: 4 months after treatment

Population: Number of subjects in each group remaining at the end of 4 months of treatment.

Rates of fatty acid oxidation were measured in breath samples following stable isotope infusions of 13C-labeled palmitate.

Outcome measures

Outcome measures
Measure	Placebo Injection n=6 Participants Each subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Placebo : Placebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.	Human Recombinant Leptin (Metreleptin) n=8 Participants Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Human recombinant leptin ("metreleptin") : Metreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
Rates of Fatty Acid Oxidation	0.239 mmol FFA/kg/h Standard Error 0.023	0.214 mmol FFA/kg/h Standard Error 0.040

SECONDARY outcome

Timeframe: 4 months after treatment.

Population: Number of subjects in each group remaining after 4 months of treatment.

Fasting plasma non-HDL-cholesterol was calculated from measured total cholesterol and HDL cholesterol.

Outcome measures

Outcome measures
Measure	Placebo Injection n=6 Participants Each subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Placebo : Placebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.	Human Recombinant Leptin (Metreleptin) n=8 Participants Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Human recombinant leptin ("metreleptin") : Metreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
Fasting Plasma Non-HDL-C	136 mg/dL Standard Error 9	127 mg/dL Standard Error 7

SECONDARY outcome

Timeframe: 4 months after treatment.

Population: Number of subjects remaining after 4 months of treatment.

An oral glucose tolerance test was performed. This is not PD/PK in the sense that we are not studying the distribution or clearance of a drug. Rather, we are performing a standard clinical test of glucose tolerance. i.e., a test for diabetes and pre-diabetes. Although multiple time points are used in this test, the outcome is a single value, either a blood glucose level after 2 hours or an area-under-the-curve. In this study we are reporting the area-under-the-curve.

Outcome measures

Outcome measures
Measure	Placebo Injection n=4 Participants Each subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Placebo : Placebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.	Human Recombinant Leptin (Metreleptin) n=5 Participants Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Human recombinant leptin ("metreleptin") : Metreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
Glucose Levels After Glucose Challenge	6268 mg/dL Standard Error 434	6647 mg/dL Standard Error 514

SECONDARY outcome

Timeframe: 4 months after treatment.

Population: Number of subjects remaining after 4 months of treatment.

An oral glucose tolerance test was performed to measure endogenous insulin response. This is not PD/PK in the sense that we are not studying the distribution or clearance of a drug. Rather, we are performing a clinical test of endogenous insulin response to glucose i.e., an endocrine test. Although multiple time points are used in this test, the outcome is a single value, i.e., an area-under-the-curve for insulin.

Outcome measures

Outcome measures
Measure	Placebo Injection n=4 Participants Each subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Placebo : Placebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.	Human Recombinant Leptin (Metreleptin) n=5 Participants Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Human recombinant leptin ("metreleptin") : Metreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
Insulin Levels After Oral Glucose Challenge.	1580 microU/mL Standard Error 954	2868 microU/mL Standard Error 890

Adverse Events

Placebo Injection

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Human Recombinant Leptin (Metreleptin)

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Injection n=8 participants at risk Each subject will receive placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months. Placebo : Placebo will administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.	Human Recombinant Leptin (Metreleptin) n=9 participants at risk Each subject will receive 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months. Human recombinant leptin ("metreleptin") : Metreleptin will be administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
Metabolism and nutrition disorders Hyperthyroidism	12.5% 1/8 • Number of events 1 • The duration of the study for each subject was 4 months. However, due to slow recruitment the entire study took place over approximately 4 years; therefore the average duration of subject follow-up for Adverse Events was approximately 2 years	0.00% 0/9 • The duration of the study for each subject was 4 months. However, due to slow recruitment the entire study took place over approximately 4 years; therefore the average duration of subject follow-up for Adverse Events was approximately 2 years
Metabolism and nutrition disorders Weight loss	0.00% 0/8 • The duration of the study for each subject was 4 months. However, due to slow recruitment the entire study took place over approximately 4 years; therefore the average duration of subject follow-up for Adverse Events was approximately 2 years	22.2% 2/9 • Number of events 2 • The duration of the study for each subject was 4 months. However, due to slow recruitment the entire study took place over approximately 4 years; therefore the average duration of subject follow-up for Adverse Events was approximately 2 years

Other adverse events

Adverse event data not reported

Additional Information

Leanne Scott, PhD, Director of Sponsored Programs

Baylor College of Medicine

Phone: 713-798-6978

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place