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Effects of Sitagliptin (Januvia®) on Blood Glucose Control in Patients With Type 1 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Satish K. Garg, University of Colorado Denver School of Medicine Barbara Davis Center
ClinicalTrials.gov Identifier:
NCT01227460
First received: October 22, 2010
Last updated: April 3, 2013
Last verified: April 2013
History of Changes
  Purpose

This is a multi-center, prospective, randomized, double-blind, parallel, placebo controlled clinical trial evaluating the efficacy of sitagliptin in suppressing glucagon release in subjects with type 1 diabetes over a 16 week treatment period. The hypothesis of this study is that sitagliptin (Januvia™) will decrease post-prandial glucagon release and may result in improved glucose control in adult patients with type 1 diabetes. There is only one small, pilot study of sitagliptin in patients with type 1 diabetes which significantly reduced total daily insulin dose and A1c values while improving mean blood glucose (MBG) and time spent in euglycemic range (1). In the pilot study, GLP-1 and glucagon levels were not assessed. The purpose of this trial is to determine if sitagliptin can suppress the paradoxical rise of glucagon, and thus can decrease A1c.

This study will enroll a maximum of 140 patients (with an expected 10% dropout rate) with A1c values between 7.5-10% who will be randomized in a 1:1 fashion to either the study drug or placebo. 100 of these patients will wear a continuous glucose monitor. Subjects may be using insulin via continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). The clinic visits will be conducted at screening, -1 week, baseline/randomization, 4 weeks, 12 weeks, and 16 weeks in addition to telephone visits (Appendix 1 and 2). At home, starting at week 0 (randomization/baseline), subjects will take 100 mg/day of sitagliptin or placebo and continue for the study duration. Laboratory analysis will be performed at various time points assessing glucagon, A1c, C-peptide, glucagon-like-peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and insulin levels.


Condition Intervention
Type 1 Diabetes
 Drug: Sitagliptin
Drug: Sugar Pill

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: Effects of Sitagliptin (Januvia®) on Blood Glucose Control in Patients With Type 1 Diabetes and CGM Substudy of the Investigator Initiated Study Protocol Effects of Sitagliptin (Januvia) on Glucagon Suppression and GLP-1 Levels in Patients With Type 1 Diabetes; CGM Substudy

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Colorado Denver School of Medicine Barbara Davis Center:

Primary Outcome Measures:
  • To demonstrate a decrease in post-prandial glucagon release as assessed by glucagon area under the curve (AUC) for 3 hours during 4 hour meal tolerance tests [ Time Frame: Primary outcome meausre will be recoreded after 16 weeks of treatment ] [ Designated as safety issue: Yes ]
    To demonstrate a decrease in post-prandial glucagon release as assessed by glucagon area under the curve (AUC) for 3 hours during 4 hour meal tolerance tests


Secondary Outcome Measures:
  • Secondary objectives: 1. To demonstrate a 0.3% decrease in A1c in patients with type 1 diabetes after 16 weeks of treatment with sitagliptin. 2. To evaluate changes in total, basal and bolus insulin dose while on sitagliptin. [ Time Frame: Secondary outcome meausre will be recoreded after 16 weeks of treatment ] [ Designated as safety issue: Yes ]

    Secondary objectives:

    1. To demonstrate a 0.3% decrease in A1c in patients with type 1 diabetes after 16 weeks of treatment with sitagliptin.
    2. To evaluate changes in total, basal and bolus insulin dose while on sitagliptin.


Enrollment: 140
Study Start Date: November 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin Drug: Sitagliptin
pill/tablet form of 100mg each. will take one tablet a day throughout study
Placebo Comparator: Sugar Pill Drug: Sugar Pill
100mg tablet once a day

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent before any study-related activities
  • Male or female aged 18 to 70 years
  • Type 1 diabetes mellitus duration > 1 year
  • Treatment with MDI or CSII therapy for at least 3 months prior to screening visit; stable insulin dose for the last 1 month
  • No use of pramlintide, saxagliptin, metformin or sitagliptin for 1 month prior to enrollment
  • A1c 7.5-10%
  • Willingness to routinely practice at least 2-4 blood glucose measurements per day
  • BMI ≤ 35 kg/m2
  • Ability and willingness to adhere to the protocol including daily oral dose of study drug or placebo and week-long CGM wear
  • Willing to complete phone and clinic visits
  • Ability to speak, read and write English

Exclusion Criteria:

  • Use of oral, inhaled or pre-mixed insulin
  • Pregnant or intention to become pregnant during the course of the study not using adequate birth control methods
  • Severe unexplained hypoglycemia requiring emergency treatment in the previous 3 months
  • Use of systemic or inhaled corticosteroids
  • History of hemoglobinopathies
  • Diagnosis of anemia
  • Post-renal transplantation, currently undergoing dialysis, creatinine >2.0 mg/dl or a calculated creatinine clearance of <50 mL/min
  • Advanced retinopathy needing laser procedure or vitrectomy
  • History of pancreatitis
  • Extensive skin changes/diseases that inhibit wearing a sensor on normal skin
  • Known allergy to adhesives
  • Known allergy to study medication
  • Participation in another investigational study protocol within 30 days prior to enrollment
  • Any other condition, as determined by the investigator, which could make the subject unsuitable for the trial, impairs the subject's suitability for the trial, or impairs the validity of the informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01227460

Locations
United States, Colorado
University of Colorado/Barbara Davis Center for Diabetes
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado Denver School of Medicine Barbara Davis Center
Investigators
Principal Investigator: Satish K Garg, MD University of Colorado Denver, Barbara Davis Center
  More Information

Publications:

Responsible Party: Satish K. Garg, Professor of Medicine and Pediatrics, University of Colorado Denver School of Medicine Barbara Davis Center
ClinicalTrials.gov Identifier: NCT01227460     History of Changes
Other Study ID Numbers: MRK-SI-100
Study First Received: October 22, 2010
Last Updated: April 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado Denver School of Medicine Barbara Davis Center:
Type 1 diabetes, Sitagliptin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Sitagliptin
 Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013