Effects of Leptin Replacement in Children

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT00659828
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 1
• Location: 1
• Arm: 1
• Actual Duration (Months): 58.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity; Metabolic Syndrome; Diabetes	Drug: Recombinant methionyl human leptin	Phase 2

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Leptin Replacement in Children
• Actual Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Apr 16, 2010
• Actual Study Completion Date: Apr 16, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Recombinant Methionyl Human Leptin 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; Recombinant methionyl human leptin, subcutaneous, once a day, 0.02 to 0.04 mg/kg (adjusted according to weight loss), indeterminate duration.; Other Names: Metreleptin r-metHuLeptin

Outcome Measures

Primary Outcome Measures

1. Weight [Baseline, 58 months]

Secondary Outcome Measures

1. Glucose Levels [Baseline, 58 months]

2. Bone Mineral Density [Baseline, 58 months]

Eligibility Criteria

Criteria

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

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

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, 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: Richard Bookman, Associate Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT00659828
• Other Study ID Numbers: 20060295; 2R01DK058851-03
• First Posted: Apr 16, 2008
• Last Update Posted: Feb 13, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Richard Bookman, Associate Professor, University of Miami: Congenital leptin deficiency; Obesity; Metabolic Syndrome; Diabetes
• Additional relevant MeSH terms: Metabolic Syndrome

Study Results

Participant Flow

Arm/Group Title	Recombinant Methionyl Human Leptin
Arm/Group Description	Recombinant methionyl human leptin: Recombinant methionyl human leptin, subcutaneous, once a day, 0.02 to 0.04 mg/kg (adjusted according to weight loss).
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Recombinant Methionyl Human Leptin
Arm/Group Description	Recombinant methionyl human leptin: Recombinant methionyl human leptin, subcutaneous, once a day, 0.02 to 0.04 mg/kg (adjusted according to weight loss).
Overall Participants	1
Age (Count of Participants)
<=18 years	1 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	1 100%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Weight
Time Frame	Baseline, 58 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Recombinant Methionyl Human Leptin
Arm/Group Description	Recombinant methionyl human leptin: Recombinant methionyl human leptin, subcutaneous, once a day, 0.02 to 0.04 mg/kg (adjusted according to weight loss).
Measure Participants	1
Number [lbs]	NA

2. Secondary Outcome

Title	Glucose Levels
Time Frame	Baseline, 58 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Recombinant Methionyl Human Leptin
Arm/Group Description	Recombinant methionyl human leptin: Recombinant methionyl human leptin, subcutaneous, once a day, 0.02 to 0.04 mg/kg (adjusted according to weight loss).
Measure Participants	1
Number [mg/dL]	NA

3. Secondary Outcome

Title	Bone Mineral Density
Time Frame	Baseline, 58 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Recombinant Methionyl Human Leptin
Arm/Group Description	Recombinant methionyl human leptin: Recombinant methionyl human leptin, subcutaneous, once a day, 0.02 to 0.04 mg/kg (adjusted according to weight loss).
Measure Participants	1
Number [g/cm^2]	NA

Adverse Events

Time Frame	4 years and 10 months
Adverse Event Reporting Description	Adverse Events not reported due to participant confidentiality.
Arm/Group Title	Recombinant Methionyl Human Leptin
Arm/Group Description	Recombinant methionyl human leptin: Recombinant methionyl human leptin, subcutaneous, once a day, 0.02 to 0.04 mg/kg (adjusted according to weight loss).
All Cause Mortality
	Recombinant Methionyl Human Leptin
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Recombinant Methionyl Human Leptin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Recombinant Methionyl Human Leptin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.