Effects of Leptin Replacement in Children

NCT00659828 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 200602952R01DK058851-03
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the endocrine and immune effects of leptin replacement in leptin-deficient children, from a consanguineous family. The hypothesis is that leptin replacement will have significant effects on endocrine function.

Conditions

Obesity; Metabolic Syndrome; Diabetes

Keywords

Congenital leptin deficiency; Obesity; Metabolic Syndrome; Diabetes

Outcome Measures

Primary Outcomes (1)

• Weight

  Baseline, 58 months

Secondary Outcomes (2)

• Glucose Levels

  Baseline, 58 months

• Bone Mineral Density

  Baseline, 58 months

Study Arms (1)

Recombinant Methionyl Human Leptin

EXPERIMENTAL

Recombinant methionyl human leptin: Recombinant methionyl human leptin, subcutaneous, once a day, 0.02 to 0.04 mg/kg (adjusted according to weight loss).

Drug: Recombinant methionyl human leptin

Interventions

Recombinant methionyl human leptin DRUG

Recombinant methionyl human leptin, subcutaneous, once a day, 0.02 to 0.04 mg/kg (adjusted according to weight loss), indeterminate duration.

Also known as: Metreleptin, r-metHuLeptin

Recombinant Methionyl Human Leptin

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children with a functional leptin gene mutation from a consanguineous Turkish family. Only one leptin-naïve child from this family is alive and eligible.

You may not qualify if:

• N/A

Sponsors & Collaborators

• University of Miami: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Miami, Center on Pharmacogenomics

Miami, Florida, 33132, United States

Location

Related Publications (13)

• Baicy K, London ED, Monterosso J, Wong ML, Delibasi T, Sharma A, Licinio J. Leptin replacement alters brain response to food cues in genetically leptin-deficient adults. Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18276-9. doi: 10.1073/pnas.0706481104. Epub 2007 Nov 6.

  PMID: 17986612 BACKGROUND

• Licinio J, Ribeiro L, Busnello JV, Delibasi T, Thakur S, Elashoff RM, Sharma A, Jardack PM, Depaoli AM, Wong ML. Effects of leptin replacement on macro- and micronutrient preferences. Int J Obes (Lond). 2007 Dec;31(12):1859-63. doi: 10.1038/sj.ijo.0803703. Epub 2007 Aug 7.

  PMID: 17684509 BACKGROUND

• Licinio J, Milane M, Thakur S, Whelan F, Yildiz BO, Delibasi T, de Miranda PB, Ozata M, Bolu E, Depaoli A, Wong ML. Effects of leptin on intake of specific micro- and macronutrients in a woman with leptin gene deficiency studied off and on leptin at stable body weight. Appetite. 2007 Nov;49(3):594-9. doi: 10.1016/j.appet.2007.03.228. Epub 2007 Apr 6.

  PMID: 17517446 BACKGROUND

• Williamson DA, Ravussin E, Wong ML, Wagner A, Dipaoli A, Caglayan S, Ozata M, Martin C, Walden H, Arnett C, Licinio J. Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy. Appetite. 2005 Aug;45(1):75-80. doi: 10.1016/j.appet.2005.01.002.

  PMID: 15949871 BACKGROUND

• Matochik JA, London ED, Yildiz BO, Ozata M, Caglayan S, DePaoli AM, Wong ML, Licinio J. Effect of leptin replacement on brain structure in genetically leptin-deficient adults. J Clin Endocrinol Metab. 2005 May;90(5):2851-4. doi: 10.1210/jc.2004-1979. Epub 2005 Feb 15.

  PMID: 15713712 BACKGROUND

• Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O'Kirwan F, Whitby R, Liang L, Cohen P, Bhasin S, Krauss RM, Veldhuis JD, Wagner AJ, DePaoli AM, McCann SM, Wong ML. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4531-6. doi: 10.1073/pnas.0308767101. Epub 2004 Mar 9.

  PMID: 15070752 BACKGROUND

• Mantzoros CS, Ozata M, Negrao AB, Suchard MA, Ziotopoulou M, Caglayan S, Elashoff RM, Cogswell RJ, Negro P, Liberty V, Wong ML, Veldhuis J, Ozdemir IC, Gold PW, Flier JS, Licinio J. Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans. J Clin Endocrinol Metab. 2001 Jul;86(7):3284-91. doi: 10.1210/jcem.86.7.7644.

  PMID: 11443202 BACKGROUND

• Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab. 1999 Oct;84(10):3686-95. doi: 10.1210/jcem.84.10.5999.

  PMID: 10523015 BACKGROUND

• Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet. 1998 Mar;18(3):213-5. doi: 10.1038/ng0398-213. No abstract available.

  PMID: 9500540 BACKGROUND

• Paz-Filho G, Wong ML, Licinio J. The procognitive effects of leptin in the brain and their clinical implications. Int J Clin Pract. 2010 Dec;64(13):1808-12. doi: 10.1111/j.1742-1241.2010.02536.x.

  PMID: 21070531 DERIVED

• Paz-Filho GJ, Delibasi T, Erol HK, Wong ML, Licinio J. Cellular immunity before and after leptin replacement therapy. J Pediatr Endocrinol Metab. 2009 Nov;22(11):1069-74. doi: 10.1515/jpem.2009.22.11.1069.

  PMID: 20101893 DERIVED

• Paz-Filho G, Delibasi T, Erol HK, Wong ML, Licinio J. Congenital leptin deficiency and thyroid function. Thyroid Res. 2009 Nov 4;2(1):11. doi: 10.1186/1756-6614-2-11.

  PMID: 19889232 DERIVED

• Paz-Filho GJ, Babikian T, Asarnow R, Delibasi T, Esposito K, Erol HK, Wong ML, Licinio J. Leptin replacement improves cognitive development. PLoS One. 2008 Aug 29;3(8):e3098. doi: 10.1371/journal.pone.0003098.

  PMID: 18769731 DERIVED

MeSH Terms

Conditions

Obesity; Metabolic Syndrome; Diabetes Mellitus

Interventions

recombinant methionyl human leptin; metreleptin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

This is a compassionate use study for a rare disease population. To protect participant privacy and maintain confidentiality, results will not be reported.

Results Point of Contact

• Title: Richard Bookman
• Organization: University of Miami

y.p.davis@med.miami.edu

305-243-0494

Study Officials

• Julio Licinio, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 9, 2008
• First Posted: April 16, 2008
• Study Start: June 1, 2005
• Primary Completion: April 16, 2010
• Study Completion: April 16, 2010
• Last Updated: February 13, 2020
• Results First Posted: February 13, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)