Trial of Leptin Administration After Roux-en-Y Gastric Bypass

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00710814
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Amylin Pharmaceuticals, LLC. (Industry), National Center for Research Resources (NCRR) (NIH)
• Enrollment: 31
• Location: 1
• Arms: 2
• Duration (Months): 75
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a pilot and feasibility study to examine a novel intervention using leptin in weight-reduced individuals who have undergone bariatric surgery but still remain obese. Leptin, a peptide hormone secreted from adipose tissue, is a regulator of food intake and energy expenditure. Administration of leptin resulted in profound weight reduction in the few reported cases of obese individuals with genetic leptin deficiency. However, most obese people have increased leptin levels. Such individuals are said to be in a "leptin-resistant" state, whereby administration of physiological concentrations of leptin are ineffective at producing significant weight reduction. Roux-en-Y gastric bypass surgery (RYGBP) is more effective than diet alone in producing long-term reduction of body weight. Yet even after surgery there is a plateau in weight loss though the individual may still be obese and have or be at risk for obesity related morbidities. The investigators have shown that plasma leptin levels are significantly lower in women after RYGBP compared with BMI-matched controls. This state of relative hypoleptinemia or leptin insufficiency suggests that post-RYGBP individuals may be in a "leptin-sensitive" state and, thus, would undergo further weight loss when administered doses of leptin that would not normally result in significant weight reduction. This study will examine the effects of leptin administered by self-injection twice per day on body weight and endocrine function. All individuals will received leptin and placebo and different times during the 34 week study period.

Condition or Disease	Intervention/Treatment	Phase
Overweight	Drug: Leptin; Other: Placebo	Phase 1/Phase 2

Detailed Description

Metreleptin will be self-administered by subcutaneous injection at 0.05 mg/kg body weight twice per day (i.e. at 8 am and 8 pm). This dose was chosen because it would not be expected to cause substantial weight loss in an obese non-surgical population, nor should it incur any substantial injection site reactions. Subjects will receive a demonstration of dose preparation and injection in addition to written instructions with visual aides. After the run-in period, subjects will demonstrate their preparation and injection technique. Placebo injections will consist of sterile water equal in volume to that of the metreleptin dose calculated for each individual. Subjects will be instructed to continue with their current level of physical activity. At week 16, each subject will cross-over to the alternate treatment for an additional 16 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of Leptin on Body Weight and Neuroendocrine Axes After Gastric Bypass
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Leptin - Placebo Leptin self-administered subcutaneously twice each day for 16 weeks, then Placebo for 16 weeks.	Drug: Leptin; Leptin self-administered subcutaneously at 0.05 mg/kg body weight twice each day; Other Names: metreleptin ; Other: Placebo; Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day
Placebo Comparator: Placebo - Leptin Placebo self-administered subcutaneously twice each day for 16 weeks, then Leptin for 16 weeks.	Drug: Leptin; Leptin self-administered subcutaneously at 0.05 mg/kg body weight twice each day; Other Names: metreleptin ; Other: Placebo; Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day

Outcome Measures

Primary Outcome Measures

1. Weight Change (in kg.) After Each Intervention [0 weeks, 16 weeks and 32 weeks]

   For the Leptin Intervention, 16 week values were compared to baseline for those who received Leptin in the first period, and 32 week values were compared to 16 week values in those who received Leptin in the second period. For the Placebo Intervention, 16 week values were compared to baseline for those who received Placebo in the first period, and 32 week values were compared to 16 week values in those who received Placebo in the second period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women ages 25-65 years who are 18 months to 15 years Roux-en-Y gastric bypass

• Current BMI of 28-50 kg/m2 and a percent total body weight loss from highest pre-surgical weight of >20% and <45%

• Must live in the vicinity of New York City to comply with 11 study visits over 34 weeks

• Must be willing to self-inject study drug twice per day

Exclusion Criteria:

• Diabetes

• History of plastic surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Amylin Pharmaceuticals, LLC.
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Judith Korner, MD,PhD, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Judith Korner, Associate Professor of Medicine, Columbia University
• ClinicalTrials.gov Identifier: NCT00710814
• Other Study ID Numbers: AAAC6692; R21DK081050; UL1RR024156
• First Posted: Jul 4, 2008
• Last Update Posted: Nov 16, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Judith Korner, Associate Professor of Medicine, Columbia University: Roux-en-Y gastric bypass; Leptin; Bariatric surgery; Overweight after Roux-en-Y gastric bypass surgery
• Additional relevant MeSH terms: Overweight

Study Results

Participant Flow

Arm/Group Title	Leptin-Placebo	Placebo-Leptin
Arm/Group Description	Leptin self-administered subcutaneously twice each day for 16 weeks, then Placebo for 16 weeks.	Placebo self-administered subcutaneously twice each day for 16 weeks, then Leptin for 16 weeks.
Period Title: Overall Study
STARTED	15	16
COMPLETED	14	13
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Leptin - Placebo	Placebo - Leptin	Total
Arm/Group Description	Leptin self-administered subcutaneously twice each day for 16 weeks, then Placebo for 16 weeks.	Placebo self-administered subcutaneously twice each day for 16 weeks, then Leptin for 16 weeks.	Total of all reporting groups
Overall Participants	15	16	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	16 100%	31 100%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	50.93	42.76	47
Sex: Female, Male (Count of Participants)
Female	15 100%	16 100%	31 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%	16 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Weight Change (in kg.) After Each Intervention
Description	For the Leptin Intervention, 16 week values were compared to baseline for those who received Leptin in the first period, and 32 week values were compared to 16 week values in those who received Leptin in the second period. For the Placebo Intervention, 16 week values were compared to baseline for those who received Placebo in the first period, and 32 week values were compared to 16 week values in those who received Placebo in the second period.
Time Frame	0 weeks, 16 weeks and 32 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Leptin Intervention	Placebo Intervention
Arm/Group Description	Participants in the Leptin-Placebo arm were randomized to first receive Leptin for the first 16 weeks, and participants in the Placebo-Leptin arm were randomized to receive Leptin for the second 16 weeks. Both Leptin and placebo were self-administered subcutaneously twice per day.	Participants in the Placebo-Leptin arm were randomized to receive placebo for the first 16 weeks, and participants in the Leptin-Placebo arm were randomized to receive placebo for the second 16 weeks. Both Leptin and placebo were self-administered subcutaneously twice per day.
Measure Participants	27	27
Mean (95% Confidence Interval) [kg weight change]	-0.39	0.02

Adverse Events

Time Frame	32 Weeks
Arm/Group Title	Leptin Intervention		Placebo Intervention
Arm/Group Description	This group "Leptin Intervention" inlcudes the adverse events that were observed while the subjects in either crossover arms when they received Leptin only.		This group "Placebo Intervention" inlcudes the adverse events that were observed while the subjects in either crossover arms when they received Placebo only.
All Cause Mortality
	Leptin Intervention		Placebo Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Leptin Intervention		Placebo Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Leptin Intervention		Placebo Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/27 (33.3%)		4/27 (14.8%)
Skin and subcutaneous tissue disorders
Itchiness and bruising at injection site	9/27 (33.3%)	9	0/27 (0%)	0
Bruising at injection site	0/27 (0%)	0	4/27 (14.8%)	4

Limitations/Caveats

[Not Specified]

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.