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

NCT ID: NCT02127047

Last Updated: 2017-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2016-08-05

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sitagliptin

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

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

Sitagliptin and exercise

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

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

Exercise

Intervention Type: DRUG

Interventions

Sitagliptin

Intervention Type: DRUG

Exercise

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Type 1 diabetes (American Diabetes Association criteria) of > 2 year duration that is judged to be stable by the investigator

2. No clinically significant change in treatment regimen for type 1 diabetes (defined as a 20% change) during the 3 months prior to Screening

3. Positive glutamic acid decarboxylase 65 and/or Islet Antigen (IA)-2 auto-antibodies

4. Age ≥ 18 years and ≤ 55 years

5. HbA1c < 7.5% for the previous two measurements including the measurement taken at Screening (both measurements must occur within 6 months prior to enrollment)

6. Body-mass index (BMI) > 18 and < 28 kg/m2

7. Willingness to maintain current doses/regimens of vitamins and dietary supplements through the end of the study

8. 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.

Exclusion Criteria

1. Regular training of more than 90 minutes / week

2. History or signs of cardiovascular disease, proliferative retinopathy, nephropathy or neuropathy

3. Signs of current infection

4. Neutropenia

5. Anemia

6. Clinically significant kidney or liver disease

7. Current immunosuppressive treatment or documented immunodeficiency

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Donath, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

University Hospital Basel

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

EKBB 349/12

Identifier Type: -

Identifier Source: org_study_id