NCT01778556

Short-term Effects of Leptin in People With Lipodystrophy

Completed Phase 2 Results posted Last updated 13 November 2019

What this trial tests

Phase 2 trial testing Metreleptin in Lipodystrophy in 25 participants. Completed in 23 February 2018.

Timeline

26 January 2013

Primary endpoint
23 February 2018

23 February 2018

Quick facts

Lead sponsor	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	25
Start date	26 January 2013
Primary completion	23 February 2018
Estimated completion	23 February 2018
Sites	1 location across United States

Drugs / interventions tested

• Metreleptin (METRELEPTIN) — full drug profile →

Conditions studied

• Lipodystrophy — all drugs for Lipodystrophy →

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Who can join

Adults 14 to 70, any sex, with Lipodystrophy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Total Body Insulin Sensitivity Primary · Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)

Total body insulin sensitivity (measured as glucose disposal rate during a hyperinsulinemic, euglycemic clamp)

Intervention 1 (5 days)

Group	Value	95% CI
Leptin Naive	4.4	± 2.3
On-leptin	10.9	± 4.1

Intervention 2 (14 days)

Group	Value	95% CI
Leptin Naive	5.8	± 2.2
On-leptin	6.4	± 1.8

Long-term follow-up (6 months)

Group	Value	95% CI
Leptin Naive	8.0	± 4.0

Insulin-mediated Suppression of Hepatic Glucose Production Secondary · Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)

Hepatic insulin sensitivity (measured as suppression of endogenous glucose production during a hyperinsulinemic, euglycemic clamp)

Intervention 1 (5 days)

Group	Value	95% CI
Leptin Naive	61.2	± 23.4
On-leptin	77.1	± 42.7

Intervention 2 (14 days)

Group	Value	95% CI
Leptin Naive	75.2	± 33.1
On-leptin	63.8	± 31.7

Long-term follow-up (6 months)

Group	Value	95% CI
Leptin Naive	85.6	± 17.9

Endogenous Rate of Appearance of Palmitate Secondary · Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)

Endogenous Rate of Appearance of Palmitate is measured in plasma.

Intervention 1 (5 days)

Group	Value	95% CI
Leptin Naive	3.2	± 1.3
On-leptin	1.4	± 0.7

Intervention 2 (14 days)

Group	Value	95% CI
Leptin Naive	2.8	± 1.0
On-leptin	1.7	± 0.6

Long-term follow-up (6 months)

Group	Value	95% CI
Leptin Naive	2.2	± 0.7

Adverse events — posted to ClinicalTrials.gov

Time frame: 6 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Intervention 1 (5 Days) : Leptin Naive

Serious: 0/15 (0%)

Deaths: 0/15

Intervention 2 (14 Days): Leptin Naive

Serious: 1/15 (7%)

Deaths: 0/15

Long-term Follow-up (6 Months): Leptin Naive

Serious: 2/15 (13%)

Deaths: 0/15

Intervention 1 ( 5 Days) : On-Leptin

Serious: 0/8 (0%)

Deaths: 0/8

Intervention 1 ( 14 Days): On-Leptin

Serious: 0/8 (0%)

Deaths: 0/8

Serious adverse events (3 terms)

Reaction	System	Intervention 1 (5 Days) : …	Intervention 2 (14 Days): …	Long-term Follow-up (6 Mon…	Intervention 1 ( 5 Days) :…	Intervention 1 ( 14 Days):…
abdominal pain of unknown etiology	Gastrointestinal disorders	—	—	—	—	—
angioedema secondary to angiotensin- converting enzyme inhibitor use	Cardiac disorders	—	—	—	—	—
anemia secondary to menorrhagia	Endocrine disorders	—	—	—	—	—

Other adverse events (6 terms — click to expand)

Reaction	System	Intervention 1 (5 Days) : …	Intervention 2 (14 Days): …	Long-term Follow-up (6 Mon…	Intervention 1 ( 5 Days) :…	Intervention 1 ( 14 Days):…
decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
weight loss	Metabolism and nutrition disorders	—	—	—	—	—
hair loss	Skin and subcutaneous tissue disorders	—	—	—	—	—
hypoglycemia (in a subject treated with insulin)	Metabolism and nutrition disorders	—	—	—	—	—
injection site reaction	Injury, poisoning and procedural complications	—	—	—	—	—
menorrhagia	Endocrine disorders	—	—	—	—	—

Most-reported serious reactions: abdominal pain of unknown etiology, angioedema secondary to angiotensin- converting enzyme inhibitor use, anemia secondary to menorrhagia.

Data from ClinicalTrials.gov NCT01778556 adverse events section.

Sponsor's own description

Background:

\- Lipodystrophy is a condition where people do not have enough fat in the body. People with lipodystrophy can have problems such as diabetes or an enlarged liver. Researchers are looking at how leptin, a hormone produced by fat cells, can help people with these problems. Leptin helps control appetite and how the body stores food. Taking leptin can help people with lipodystrophy eat less food, which may help treat diabetes and other problems. To better understand how leptin works, researchers want to do an inpatient study on leptin treatment in people with lipodystrophy.

Objectives:

\- To study how leptin treatment affects lipodystrophy.

Eligibility:

\- Individuals between 14 and 70 years of age who have lipodystrophy.

Design:

* All participants will have a 19-day stay at the National Institutes of Health Clinical Center. One group of participants will have tests for 5 days before starting to take leptin. They will then take leptin for 2 weeks, and have more tests. The other group of participants will have tests for 5 days while taking leptin. They will then take stop taking leptin for 2 weeks, and have more tests, and then they will start taking leptin again.
* Participants will have regular blood and urine tests during the visit. Some of the blood tests will look at insulin levels. Some will look at how the body metabolizes sugar and fat. Other tests will check hormone levels, especially of reproductive hormones.
* During the visit, participants will spend 3 separate days in a metabolic chamber, a special room that measures how many calories the body uses. Urine samples will be collected during these stays.
* Participants will also have several body imaging studies, including magnetic resonance imaging and a body composition scan.
* Physical activity will be tested with an exercise bicycle and an electronic activity monitor.
* Participants will be asked questions about hunger and comfort levels throughout the stay.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy.
   Brown RJ, Valencia A, Startzell M, Cochran E, et al · · 2018 · cited 76× · PMID 29723161 · DOI 10.1172/jci95476
2. Free fatty acid processing diverges in human pathologic insulin resistance conditions.
   Sekizkardes H, Chung ST, Chacko S, Haymond MW, et al · · 2020 · cited 48× · PMID 32191645 · DOI 10.1172/jci135431
3. Effects of Metreleptin in Pediatric Patients With Lipodystrophy.
   Brown RJ, Meehan CA, Cochran E, Rother KI, et al · · 2017 · cited 44× · PMID 28324110 · DOI 10.1210/jc.2016-3628
4. Efficacy of Metreleptin Treatment in Familial Partial Lipodystrophy Due to PPARG vs LMNA Pathogenic Variants.
   Sekizkardes H, Cochran E, Malandrino N, Garg A, et al · · 2019 · cited 34× · PMID 31194872 · DOI 10.1210/jc.2018-02787
5. Leptin decreases de novo lipogenesis in patients with lipodystrophy.
   Baykal AP, Parks EJ, Shamburek R, Syed-Abdul MM, et al · · 2020 · cited 33× · PMID 32573497 · DOI 10.1172/jci.insight.137180
6. Advanced Lipoprotein Analysis Shows Atherogenic Lipid Profile That Improves After Metreleptin in Patients with Lipodystrophy.
   Kinzer AB, Shamburek RD, Lightbourne M, Muniyappa R, et al · · 2019 · cited 29× · PMID 31620670 · DOI 10.1210/js.2019-00103
7. Effects of Metreleptin on Patient Outcomes and Quality of Life in Generalized and Partial Lipodystrophy.
   Cook K, Adamski K, Gomes A, Tuttle E, et al · · 2021 · cited 28× · PMID 33817539 · DOI 10.1210/jendso/bvab019
8. Effect of Leptin Therapy on Survival in Generalized and Partial Lipodystrophy: A Matched Cohort Analysis.
   Cook K, Ali O, Akinci B, Foss de Freitas MC, et al · · 2021 · cited 25× · PMID 33822100 · DOI 10.1210/clinem/dgab216