Effects of Exercise and Inhibition of Dipeptidyl Peptidase-4 on Insulin Secretion in Subjects With Type 1 Diabetes

NCT02127047 | Completed Phase 2

• 1 other identifier: EKBB 349/12
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Increasing evidence suggests pancreatic islet beta-cell regeneration occurs throughout the course of the disease in patients with type 1 diabetes. Therefore, decreased beta-cell mass in type 1 diabetes may be improved through inhibition of beta-cell destruction and stimulation of proliferation, even after prolonged duration of disease. Physical activity improves insulin secretion via unknown underlying mechanisms. We recently observed that Interleukin-6 induces glucagon like Peptide (GLP)-1 production and release from the islet alpha-cell and the intestinal L-cell. Furthermore, exercise induces release of Interleukin-6 from skeletal muscle resulting in elevated circulating Interleukin-6 levels. Therefore we hypothesize that exercise-induced Interleukin-6 promotes glucagon like peptide-1 secretion from the islet α-cell and the intestinal L-cell, thereby providing a mechanism how physical activity can help maintain and improve beta-cell function in patients with type 1 diabetes. This mechanism can be enhanced by concomitant dipeptidyl peptidase-IV inhibition. Physical activity is also known to enhance insulin sensitivity and to attenuate the immune system activity. Therefore by combining physical activity and dipeptidyl peptidase-IV inhibition we aim to allow for beta-cell regeneration in a interventional randomized open-label study.

Conditions

Diabetes Mellitus Type 1

Outcome Measures

Primary Outcomes (1)

• Change in beta-cell function as derived from change in C-peptide and glucose levels during the mixed meal test

  Day 90 compared to baseline (Day 1 pre-dose)

Secondary Outcomes (15)

• Change in insulin sensitivity as derived from change in C-peptide and glucose levels during the mixed meal test

  Day 90 compared to baseline (Day 1 pre-dose)

• Change in insulin requirements: 3-day average daily insulin dose

  baseline (Day -3 through Day -1) compared to Day 90 (Day 87 through Day 89)

• Change in HbA1c levels

  baseline (Day 1 pre-dose) at Day 90

• Change in fasting glucose

  baseline (Day 1 pre-dose) at Day 90

• Change in fasting glucagon and cortisol

  baseline (Day 1 pre-dose) at Day 90

Study Arms (2)

Sitagliptin

EXPERIMENTAL

Patients receive Sitagliptin (100mg/d) without further intervention

Drug: Sitagliptin

Sitagliptin and exercise

EXPERIMENTAL

Patients receive sitagliptin (100mg/d) and follow a physical training intervention program

Drug: Sitagliptin; Drug: Exercise

Interventions

Sitagliptin DRUG

Sitagliptin; Sitagliptin and exercise

Exercise DRUG

Sitagliptin and exercise

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Type 1 diabetes (American Diabetes Association criteria) of \> 2 year duration that is judged to be stable by the investigator
• No clinically significant change in treatment regimen for type 1 diabetes (defined as a 20% change) during the 3 months prior to Screening
• Positive glutamic acid decarboxylase 65 and/or Islet Antigen (IA)-2 auto-antibodies
• Age ≥ 18 years and ≤ 55 years
• HbA1c \< 7.5% for the previous two measurements including the measurement taken at Screening (both measurements must occur within 6 months prior to enrollment)
• Body-mass index (BMI) \> 18 and \< 28 kg/m2
• Willingness to maintain current doses/regimens of vitamins and dietary supplements through the end of the study
• For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study. Adequate contraceptive measures include hormonal methods used for two or more cycles prior to Screening (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), double barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly, and condom used in conjunction with contraceptive foam or jelly), intrauterine methods (IUD), sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner), and abstinence.

You may not qualify if:

• Regular training of more than 90 minutes / week
• History or signs of cardiovascular disease, proliferative retinopathy, nephropathy or neuropathy
• Signs of current infection
• Neutropenia
• Anemia
• Clinically significant kidney or liver disease
• Current immunosuppressive treatment or documented immunodeficiency

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Sitagliptin Phosphate; Exercise

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Marc Donath, Prof. MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2014
• First Posted: April 30, 2014
• Study Start: November 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: August 5, 2016
• Last Updated: July 27, 2017

Record last verified: 2017-07

Locations

CH (1)