Treatment of Diabetes After Gastric Bypass With Sitagliptin (LAF33)

A Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Assess Efficacy, Safety and Tolerability of Sitagliptin Phosphate 100 mg as Treatment for Recurrent, Persistent or Newly Diagnosed Type 2 Diabetes After Gastric Bypass

The purpose of this study is to assess whether Januvia (sitagliptin phosphate 100mg) is safe and effective for the treatment of Type 2 Diabetes in patients who have had Gastric Bypass.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Sitagliptin phosphate; Other: Placebo

Detailed Description

Januvia (sitagliptin phosphate 100mg) is an FDA approved medication for the treatment of Type 2 Diabetes. Sitagliptin works by inhibiting the Dipeptidyl peptidase-4 enzyme, resulting in increased active glucagon-like peptide-1 (GLP-1) levels. GLP-1 is an incretin which increases post-prandial insulin secretion. Because Gastric Bypass has also been shown to increase GLP-1 levels, this study seeks to determine the additional effect of DDP-4 inhibition on glucose control in patients who have elevated incretin levels post Gastric Bypass. The study will also assess if Januvia (Sitagliptin phosphate) is safe and well tolerated in patients after Gastric Bypass.

Recruitment and data collection for this study was started at St. Luke's Hospital in New York, NY and later moved to Columbia University Medical Center in New York, NY.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York Obesity Nutrition Research Center, Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be a resident of the NYC metropolitan area or be able to come for emergency unscheduled and regular weekly meetings in Manhattan.
• HbA1c ≥ 6.5% and ≤ 8.5 % or a fasting glucose ≥ 126 mg/dL or a random glucose ≥ 200 mg/dL at least 12 months after GBP surgery confirmed by central laboratory.
• Subject is capable and willing to give informed consent.
• Subject is otherwise in good general health, based on medical history and physical examination.
• Subject is a non smoker for at least 6 months prior to study start
• Female subjects of child bearing potential must use oral, injected or implanted hormonal methods of contraception from at least the commencement of their last normal period prior to the first administration of the challenge agent. Subjects using hormonal contraception should use a barrier method in addition from the first administration of challenge agent until their next normal period following the end of the study.

Exclusion Criteria:

• History of type 1 diabetes
• Female subject is pregnant or breastfeeding.
• Recent (< 30 days) or simultaneous participation in another clinical trial.
• Any situation that can compromise the study, including serious illness or a predictable lack of cooperation from the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Sitagliptin phosphate; 100 mg/day sitagliptin phosphate (Januvia) PO once a day for 4-5 weeks	Drug: Sitagliptin phosphate; 100 mg/day orally; Other Names: Januvia
PLACEBO_COMPARATOR: Placebo; 1 Placebo pill / day PO once a day for 4-5 weeks	Other: Placebo; 1 Placebo Pill per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Postprandial Glucose Levels After Mixed Meal Test	Glucose levels were measured in study participants while fasting and periodically over 3 hours after drinking a 200 kcal mixed meal test, before and after intervention (Sitagliptin or Placebo).	Baseline and ~4 weeks
Change in Area Under the Curve (AUC) Glucose Levels After Mixed Meal Test	Glucose levels were measured in study participants while fasting and periodically over 3 hours after drinking a 200 kcal mixed meal test, before and after intervention (Sitagliptin or Placebo). AUC was measured by trapezoidal method.	Baseline and ~4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Sitagliptin vs Placebo on Satiety in Patients With Type 2 Diabetes After Gastric Bypass Surgery	Satiety levels were measured in study participants while they were fasting and periodically over a three hour period after drinking a 200 kcal meal drink, before and after intervention via a Visual Analog Scale. Participants were asked to mark on a 0 to 150 millimeter scale their response to the following question: "How full do you feel right now?" with lower scores indicating "not full at all" and higher scores indicating "extremely full."	Baseline and ~4 weeks
Occurrence of Side Effects In Relation to Sitagliptin	Side effects to Sitagliptin or Placebo were measured in study participants via Sigstad score questionnaire, while fasting and periodically during a 3 hour period after drinking a 200 kcal meal drink, before and after intervention. The Sigstad scoring system is based on the participants report of the occurrence of 16 symptoms suggestive of the dumping syndrome. Each symptom is given a different score. For example, desire to sit down (+4), breathlessness (+3), dizziness (+2), nausea (+1), vomiting (-4) etc.The scale can range from -5 to 34. Scores greater than or equal to 7, after glucose intake, are considered diagnostic of dumping syndrome.	6 weeks
Active GLP-1	Active GLP-1 (Fasting and during a Mixed Meal Test). The Change in Fasting Active GLP-1 refers to the change in fasting active GLP-1 from pre-intervention time point to post-intervention time point. The Change in Peak Active GLP-1 refers to the change in the peak active GLP-1 level from the pre-intervention time point to post-intervention time point.	Pre-Intervention and Post-Intervention

Collaborators and Investigators

• Sponsor: Blandine Laferrere
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• New York Obesity Nutrition Research Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2012
• Primary Completion (ACTUAL): August 1, 2016
• Study Completion (ACTUAL): August 1, 2016

Study Registration Dates

• First Submitted: January 13, 2012
• First Submitted That Met QC Criteria: January 18, 2012
• First Posted (ESTIMATE): January 19, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes; Sitagliptin; Januvia; Gastric-Bypass
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: AAAO1107; 0000048421 (OTHER_GRANT: Merck & Co., Inc)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No