Double-blinded, Randomized, Controlled Paired Trial Comparing Sitagliptin to Placebo in Closed Loop.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Blood Glucose Measures in Subjects Treated With Sitagliptin, Compared to the Placebo
Study Overview
Brief Summary
There are many recent advances in insulin treatment of type 1 Diabetes Mellitus (T1DM), however after a meal sugars are always a concern. There is a drug sitagliptin (Januvia) which is FDA approved to treat people with type 2 diabetes which helps correct their glucose (sugars) after meals. This study is going to test whether this drug can improve the after meal sugars in people with type 1 diabetes. To test this, you will be given a mixed meal and its effects on insulin levels. The hormones that affect blood glucose as well as your sugar levels will be measured by a series of blood tests. We will also look for high blood sugars which might occur because of food staying longer in the stomach than usual or due to the suppression of a hormone called glucagon which increases blood sugar. If you qualify, you will be given sitagliptin (Januvia) 50 mg and 100 mg dosages. You and the researchers will not know which dose you are taking at any single visit. We will first enroll 10 subjects with established type 1 Diabetes Mellitus for at least 1 year, between the ages of 18-30 years old. The first 10 patients will be evaluated for safety parameters such as ability to keep blood sugars < 70 mg/dl for at least 70% of the time, no episode of severe hypoglycemia (low blood sugars) and so on. After this safety criteria is established, we will then recruit subjects between the ages of 14-19 yrs for the next phase of the study. A total of 17 subjects were enrolled into the study.
Detailed Description
Rationale: Sitagliptin has been extensively studied in patients with type 2 Diabetes Mellitus (T2DM). Sitagliptin increases endogenous GLP-1 (Glucagon like peptide) by inhibiting the break down of an enzyme DPP-4 (Dipeptidyl Peptidase 4). GLP-1 in turn results in glucagon suppression.This mechanism is very effective in improving after meal blood sugars, not only in type 2 diabetics but also in type 1 diabetes. In this study we will test the use of sitagliptin in decreasing after meal blood sugars in the setting of closed loop.Data Safety Monitoring Board (DSMB) will meet before the initiation of the study and before children are enrolled into the study. The safety data after the meeting will be submitted to the Institutional Review Board (IRB).
Specific Aim: In the closed loop setting, to establish a safe and an effective dose of sitagliptin in type 1 diabetes (T1DM) compared to placebo and its effects in lowering the post meal glucose levels, Further to test its effects on insulin utilization , glucagon levels and gastric emptying.
Hypothesis: Post meal sugars will decrease in a dose dependent manner due to glucagon suppression when sitagliptin is used in the closed loop setting as compared to placebo.
Study Design: Following informed consent (and with appropriate subject assent), each subject with Type 1 DM will undergo 4 study visits: Screening , Part A (Placebo/Insulin) and Part B (Sitagliptin 100 mg). A randomized double-blinded 2-period cross over study trial will be used for the subjects to participate in the study . All the study subject's (18-30 yrs old) and the study staff (except one person) will be blinded to the study parts and they will do all the study Parts A and B in random order.
Montefiore Medical Center (MMC) Investigational pharmacy and one of the study staff (excluding the PI) will be un-blinded to the protocol for doing the randomization table, dispensing, checking the dose of study medication and scheduling the study visits (done by the study staff person). The participants will be admitted to the Clinical Research Center (CRC) on two occasions for the Parts A and B following the screening visit. Parts A and B are done with at least 2 weeks apart.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 14 Years to 30 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age of 14 to 30 years
- •Subjects must be otherwise healthy except for T1DM, and treated for hypothyroidism if present
- •Menstruating women must have negative pregnancy test.
- •Hemoglobin (Hb) more than 12 g/dl
Exclusion Criteria
- •Having any other chronic condition except hypothyroidism stable on medications
- •On chronic medications that may affect glucose excursions
- •Hemoglobin less than 12 g/dl
- •Positive pregnancy test (based on Urine)
- •Pregnant or lactating mothers Known allergy to Januvia-
Arms & Interventions
Part A
Placebo and Insulin monotherapy via CL
Intervention: Placebo and Insulin monotherapy via CL (Drug)
Part B
Sitagliptin and insulin/novolog via CL
Intervention: Sitagliptin and insulin/novolog via CL (Drug)
Outcomes
Primary Outcomes
Blood Glucose Measures in Subjects Treated With Sitagliptin, Compared to the Placebo
Time Frame: 18 Months
Better targeted blood glucose levels in the CL setting in the treatment arm, Sitagliptin, compared to placebo (insulin monotherapy)
Secondary Outcomes
- Measure of Glucagon Concentration in Subjects Treated With Sitagliptin, Compared to Placebo(18 months)
Investigators
Rubina Heptulla
Division Chief of Pediatric Endocrinology
Albert Einstein College of Medicine