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

Type 1 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01227460
• Other study ID #: MRK-SI-100
• Status: Completed
• Phase: N/A
• First received: October 22, 2010
• Last updated: May 19, 2014
• Start date: November 2010
• Est. completion date: July 2011

Study information

• Verified date: May 2014
• Source: University of Colorado Denver School of Medicine Barbara Davis Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Sitagliptin
pill/tablet form of 100mg each. will take one tablet a day throughout study
• Sugar Pill
100mg tablet once a day

Locations

Country	Name	City	State
United States	University of Colorado/Barbara Davis Center for Diabetes	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado Denver School of Medicine Barbara Davis Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

Garg SK, Moser EG, Bode BW, Klaff LJ, Hiatt WR, Beatson C, Snell-Bergeon JK. Effect of sitagliptin on post-prandial glucagon and GLP-1 levels in patients with type 1 diabetes: investigator-initiated, double-blind, randomized, placebo-controlled trial. End — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Primary outcome meausre will be recoreded after 16 weeks of treatment	Yes
Secondary	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.	Secondary objectives: To demonstrate a 0.3% decrease in A1c in patients with type 1 diabetes after 16 weeks of treatment with sitagliptin.; To evaluate changes in total, basal and bolus insulin dose while on sitagliptin.	Secondary outcome meausre will be recoreded after 16 weeks of treatment	Yes