Effects of Human Leptin Replacement

Obesity Clinical Trial

Official title:

Effects of Human Leptin Replacement

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00657605
• Other study ID #: 20060282
• Secondary ID: 1R0IDK58851-01
• Status: Completed
• Phase: Phase 2
• Start date: June 2001
• Est. completion date: May 4, 2010

Study information

• Verified date: February 2020
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will test the hypothesis that leptin contributes to the regulation of the dynamics of human endocrine function.

Description:

The study aims to elucidate the role of leptin in the regulation of human endocrine function approached by a carefully designed, prospective clinical study of the rapidly-sampled dynamics of endocrine rhythms during the course of leptin-replacement treatment in the only three adult individuals identified in the world so far who are leptin-naive due to a functional leptin gene mutation. A study of leptin-naive subjects avoids all confounding factors and pitfalls, because the only bioactive leptin to which they will be exposed is the exogenously administered recombinant protein. Thus, this proposal will permit us to ascertain the endocrine effects of human leptin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: May 4, 2010
• Est. primary completion date: May 4, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Congenital leptin deficiency (these are only 3 adult individuals in the world that have been identified as leptin-naïve thus far).

Exclusion Criteria:

• Pregnant, trying to become pregnant, breast-feeding an infant or sexually active women, not using contraception.

• Subjects with hemoglobin levels below 12 g/dl.

• Subjects whose body contains a ferromagnetic implanted device that might produce a safety hazard during fMRI.

Related Conditions & MeSH terms

• Diabetes
• Metabolic Syndrome
• Obesity

Intervention

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

Locations

Country	Name	City	State
United States	University of Miami Miller School of Medicine, Center on Pharmacogenomics	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. Epub 2007 Nov 6. — View Citation

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, h — View Citation

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 stabl — View Citation

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. Epub 2007 Aug 7. — View Citation

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 concentr — View Citation

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. Epub 2005 Feb 15. — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Weight		Baseline, 107 months
Secondary	Change in Glucose Levels		Baseline, 107 months