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CompletedNCT00140244Updated May 11, 2017Results posted

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

A Phase 2 interventional study of r-metHuLeptin and Placebo in HAART-induced Lipodystrophy and Metabolic Syndrome, sponsored by Beth Israel Deaconess Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-05-11.

Sponsored by Beth Israel Deaconess Medical Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
7
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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

02

Conditions studied

  • HAART-induced Lipodystrophy and Metabolic Syndrome

Keywords

  • leptin
  • lipodystrophy
  • insulin resistance
  • hyperlipidemia
  • metabolic syndrome
03

In context

Lipodystrophy

163 studies on the registry are indexed under Lipodystrophy; 11 are open to participants now.

This study's enrollment of 7 is below the median of 46 across 119 interventional studies indexed under Lipodystrophy.

Browse Lipodystrophy studies →

Lead sponsor

Beth Israel Deaconess Medical Center is the lead sponsor of 560 studies on the registry; 80 are open to participants now.

Of its 75 completed or terminated interventional studies of FDA-regulated products, 61 (81%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
7 participants (actual)

Study arms

  • Active comparator
    r-MetHuLeptin

    r-MetHuLeptin SubQ once daily

    Drug: r-metHuLeptin

  • Placebo comparator
    Placebo

    SubQ once daily

    Drug: Placebo

Interventions

  • Drugr-metHuLeptin
  • DrugPlacebo
06

What researchers measure

Primary outcomes

  1. Serum Lipid Levels

    Time frame: At the end of each two month intervention

Secondary outcomes

  1. Insulin Resistance (as Assessed by HOMA-IR)

    Time frame: At the end of each two month intervention

  2. Glycemia (as Assessed by Fasting Glucose)

    Time frame: At the end of each two month intervention

  3. Low Density Lipoprotein (LDL) Cholesterol Levels

    Time frame: At the end of each two month intervention

  4. Free Fatty Acid (FFA) Levels

    Time frame: At the end of each two month intervention

  5. Blood Pressure

    percent change in mean blood pressure

    Time frame: At the end of each two month intervention

  6. Fibrinogen

    Fibrinogen

    Time frame: At the end of each two month intervention

  7. Insulin Levels

    Time frame: At the end of each two month intervention

  8. Lean Body Mass

    lean body mass

    Time frame: At the end of each two month intervention

  9. Viral Load

    Time frame: At the end of each two month intervention

  10. CD4+ Lymphocytes

    Time frame: At the end of each two month intervention

  11. Interleukin-6 (IL-6) Levels

    Time frame: At the end of each two month intervention

  12. Hepatic Fat Content

    Time frame: At the end of each two month intervention

07

Results

Posted Apr 6, 2017

Participant flow

Intervention 1
Participant flow — Intervention 1
Milestoner-MetHuLeptin First, Then PlaceboPlacebo First, Then r-metHuLeptin
Started34
Completed34
Not completed00
Washout
Participant flow — Washout
Milestoner-MetHuLeptin First, Then PlaceboPlacebo First, Then r-metHuLeptin
Started34
Completed34
Not completed00
Intervention 2
Participant flow — Intervention 2
Milestoner-MetHuLeptin First, Then PlaceboPlacebo First, Then r-metHuLeptin
Started34
Completed32
Not completed02

Outcome measures

PrimarySerum Lipid Levels
Time frame:
At the end of each two month intervention
Reported as:
Mean · mg/dl
Serum Lipid Levels
mg/dlr-MetHuLeptinPlacebo
total cholesterol228.8 ± 13.3219.7 ± 13.1
low density lipoprotein cholesterol113.0 ± 12.7105.7 ± 3.33
triglycerides409.0 ± 88.8520.5 ± 91.1
high density lipoprotein cholesterols35 ± 2.2329.96 ± 2.25
Free fatty acids0.45 ± 0.070.61 ± 0.09
SecondaryInsulin Resistance (as Assessed by HOMA-IR)
Time frame:
At the end of each two month intervention
Reported as:
Mean · units on a scale
Insulin Resistance (as Assessed by HOMA-IR)
units on a scaler-metHuLeptinPlacebo
Insulin Resistance (as Assessed by HOMA-IR)2.52 ± 0.914.56 ± 1.43
SecondaryGlycemia (as Assessed by Fasting Glucose)
Time frame:
At the end of each two month intervention
Reported as:
Mean · mg/dl
Glycemia (as Assessed by Fasting Glucose)
mg/dlr-MetHuLeptinPlacebo
Glycemia (as Assessed by Fasting Glucose)91 ± 2.2895.6 ± 2.8
SecondaryLow Density Lipoprotein (LDL) Cholesterol Levels
Time frame:
At the end of each two month intervention
Reported as:
Mean · mg/dl
Low Density Lipoprotein (LDL) Cholesterol Levels
mg/dlr-MetHuLeptinPlacebo
Low Density Lipoprotein (LDL) Cholesterol Levels113 ± 12.7105.7 ± 3.33
SecondaryFree Fatty Acid (FFA) Levels
Time frame:
At the end of each two month intervention
Reported as:
Mean · mEq/liter
Free Fatty Acid (FFA) Levels
mEq/literr-MetHuLeptinPlacebo
Free Fatty Acid (FFA) Levels0.45 ± 0.070.61 ± 0.09
SecondaryBlood Pressure

percent change in mean blood pressure

Time frame:
At the end of each two month intervention
Reported as:
Least squares mean · percentage change of mean blood pressure
Blood Pressure
percentage change of mean blood pressurer-MetHuLeptinPlacebo
Blood Pressure3.2 ± 5.7-6.7 ± 6.4
SecondaryFibrinogen

Fibrinogen

Time frame:
At the end of each two month intervention
Reported as:
Mean · mg/dL
Fibrinogen
mg/dLr-MetHuLeptinPlacebo
Fibrinogen252.2 ± 16.3294.4 ± 14.58
SecondaryInsulin Levels
Time frame:
At the end of each two month intervention
Reported as:
Mean · mcIU/ml
Insulin Levels
mcIU/mlr-MetHuLeptinPlacebo
Insulin Levels11.6 ± 4.4620.3 ± 7.04
SecondaryLean Body Mass

lean body mass

Time frame:
At the end of each two month intervention
Reported as:
Mean · kg
Lean Body Mass
kgr-MetHuLeptinPlacebo
Lean Body Mass58.6 ± 4.4161.6 ± 4.26
SecondaryViral Load
Time frame:
At the end of each two month intervention
Reported as:
Mean · copies/ml
Viral Load
copies/mlr-MetHuLeptinPlacebo
Viral Load11345 ± 1059612367 ± 11861
SecondaryCD4+ Lymphocytes
Time frame:
At the end of each two month intervention
Reported as:
Mean · cells/mcl
CD4+ Lymphocytes
cells/mclr-MetHuLeptinPlacebo
CD4+ Lymphocytes556.6 ± 135637.2 ± 158.4
SecondaryInterleukin-6 (IL-6) Levels
Time frame:
At the end of each two month intervention
Reported as:
Mean · pg/ml
Interleukin-6 (IL-6) Levels
pg/mlr-MetHuLeptinPlacebo
Interleukin-6 (IL-6) Levels1.65 ± 0.382.14 ± 0.53
SecondaryHepatic Fat Content
Time frame:
At the end of each two month intervention
Reported as:
Mean · percentage of liver volume
Hepatic Fat Content
percentage of liver volumer-MetHuLeptinPlacebo
Hepatic Fat Content4.02 ± 3.154.01 ± 2.65

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
r-MetHuLeptin—0/5 (0%)0/5 (0%)
Placebo—0/7 (0%)0/7 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)All Study Participants
<=18 years0
Between 18 and 65 years7
>=65 years0
Age, Continuous
Age, Continuous(years)All Study Participants
Mean45.8 ± 2
Sex: Female, Male
Sex: Female, Male(Participants)All Study Participants
Female0
Male7
Region of Enrollment
Region of Enrollment(participants)All Study Participants
United States7
Body mass index
Body mass index(kg/m^2)All Study Participants
Mean22.2 ± 0.83
Fasting leptin concentration
Fasting leptin concentration(ng/ml)All Study Participants
Mean1.34 ± 0.2
triglycerides
triglycerides(mg/dl)All Study Participants
Mean530 ± 53.8
insulin
insulin(micro international units(μIU)/ml)All Study Participants
Mean11.5 ± 2.7

4 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
09

References and documents

Publications

  • Bouzoni E, Perakakis N, Connelly MA, Angelidi AM, Pilitsi E, Farr O, Stefanakis K, Mantzoros CS. PCSK9 and ANGPTL3 levels correlate with hyperlipidemia in HIV-lipoatrophy, are regulated by fasting and are not affected by leptin administered in physiologic or pharmacologic doses. Metabolism. 2022 Sep;134:155265. doi: 10.1016/j.metabol.2022.155265. Epub 2022 Jul 9. PubMed 35820631 ↗
  • Magkos F, Brennan A, Sweeney L, Kang ES, Doweiko J, Karchmer AW, Mantzoros CS. Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study. Metabolism. 2011 Jul;60(7):1045-9. doi: 10.1016/j.metabol.2010.10.002. Epub 2010 Nov 16. PubMed 21081243 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 11, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00140244
Lead sponsor
Beth Israel Deaconess Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Amgen
Responsible party
Christos Mantzoros (Professor of Medicine, Beth Israel Deaconess Medical Center) — Principal investigator
First posted
Sep 1, 2005
Start date
Dec 2001
Primary completion
Jun 2011
Completion
Jun 2011
Results posted
Apr 6, 2017
Last update
May 11, 2017
View the source record on ClinicalTrials.gov ↗

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