Effects of Leptin Replacement in Children - Full Text View

Sponsors and Collaborators:	University of Miami National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	University of Miami
ClinicalTrials.gov Identifier:	NCT00659828

Purpose

We will assess the endocrine and immune effects of leptin replacement in leptin-deficient children, from a consanguineous Turkish family. We hypothesize that leptin replacement will have significant effects on immune and endocrine function.

Condition	Intervention	Phase
Obesity Metabolic Syndrome Diabetes	Drug: Recombinant methionyl human leptin	Phase II

MedlinePlus related topics: Diabetes Obesity Obesity in Children

Drug Information available for: Leptin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Effects of Leptin Replacement in Children

Further study details as provided by University of Miami:

Primary Outcome Measures:

Weight [ Time Frame: Before and every 6 months after treatment is initiated, during 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Endocrine parameters [ Time Frame: Before and every 6 months after treatment is initiated, during 5 years ] [ Designated as safety issue: Yes ]
Bone mineral density [ Time Frame: Before and every 6 months after treatment is initiated, during 5 years ] [ Designated as safety issue: Yes ]
Immune function [ Time Frame: Before and every 6 months after treatment is initiated, during 5 years ] [ Designated as safety issue: Yes ]

Enrollment:	1
Study Start Date:	June 2005
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 1 leptin-deficient male born in 2000	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.

Detailed Description:

The proposed study of the treatment of a child with congenital leptin deficiency will permit to elucidate key aspects of human endocrine and immune function, and will give new insights on the role of leptin in human endocrine regulation.

Leptin administration in leptin-deficient children will possibly increase energy and fat metabolism by increasing sympathetic nervous system activity. To test this hypothesis, we will measure food intake, energy expenditure, body composition and sympathetic nervous system activity in patients homozygous due to a leptin gene mutation, before and throughout the leptin replacement therapy.

Leptin modulates T-cell function and affects the phagocytic activity of macrophages. Immune function will be assessed during the course of this study.

Specifically, tests for antibody, complement and phagocytic function, tests for T-cell immunity, flow cytometry, TREC PCR, thymus imaging studies will be performed. Antibody levels for pathogen organisms will be checked and the child will be vaccinated if needed.

Leptin also has important roles on thyroid, adrenal and gonadal functions. Morevover, leptin is correlated with levels of lipids, glucose and insulin. To test the effects of leptin replacement in leptin-deficient humans, endocrine and metabolic parameters will be measured, before and during treatment. Leptin determines changes on bone mineral density. To evaluate these changes, bone function and densitometry will also be assessed in this leptin deficient child. Finally, leptin may have a role in brain growth and development. We will conduct volumetric brain imaging studies in this patient during the course of leptin replacement, ensuring safe exposure to radiation. Neuropsychological evaluation will also be undertaken.

Eligibility

Ages Eligible for Study:	5 Years to 18 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

N/A

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00659828

Locations

United States, Florida
University of Miami, Center on Pharmacogenomics
Miami, Florida, United States, 33132

Sponsors and Collaborators

University of Miami

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

Investigators

Principal Investigator:

Julio Licinio, MD

University of Miami

More Information

Publications:

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.

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.

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. Epub 2007 Apr 6.

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.

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.

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. Epub 2004 Mar 9.

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.

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. Erratum in: J Clin Endocrinol Metab 2000 Jan;85(1):416.

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. No abstract available.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Paz-Filho GJ, Babikian T, Asarnow R, Esposito K, Erol HK, Wong ML, Licinio J. Leptin replacement improves cognitive development. PLoS ONE. 2008 Aug 29;3(8):e3098.

Responsible Party:	University of Miami ( Julio Licinio )
Study ID Numbers:	20060295, 2R01DK058851-03
Study First Received:	April 9, 2008
Last Updated:	April 14, 2008
ClinicalTrials.gov Identifier:	NCT00659828 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Miami:

Congenital leptin deficiency
Obesity
Metabolic Syndrome
Diabetes

Study placed in the following topic categories:

Body Weight
Signs and Symptoms
Obesity
Diabetes Mellitus

Nutrition Disorders
Overweight
Overnutrition

Additional relevant MeSH terms:

Body Weight
Signs and Symptoms
Obesity
Pathologic Processes
Disease

Syndrome
Nutrition Disorders
Overweight
Overnutrition

ClinicalTrials.gov processed this record on May 07, 2009