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

Diabetes Mellitus Type 1 Clinical Trial

— EXTYPE-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02127047
• Other study ID #: EKBB 349/12
• Status: Completed
• Phase: Phase 2
• First received: April 28, 2014
• Last updated: July 25, 2017
• Start date: November 2013
• Est. completion date: August 5, 2016

Study information

• Verified date: July 2017
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 5, 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 1
• Diabetes Mellitus, Type 1

Intervention

Drug:
• Sitagliptin

• Exercise

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	Change in HbA1c levels		baseline (Day 1 pre-dose) at Day 90
Secondary	Change in fasting glucose		baseline (Day 1 pre-dose) at Day 90
Secondary	Change in fasting glucagon and cortisol		baseline (Day 1 pre-dose) at Day 90
Secondary	Change in total number of hypoglycemic events compared to treatment groups		baseline (Day 1 pre-dose) to Day 90
Secondary	Change in markers of systemic inflammation		from baseline (Day 1 pre-dose) at Day 90
Secondary	Change in composition of immune cells		from baseline at Day 90
Secondary	Change in meal-stimulated GLP-1 and gastric inhibitory peptide		Day 90 compared to baseline
Secondary	Change in lipids profile		baseline at Day 90
Secondary	Change in fatigue according to the Fatigue Scale for Motor and Cognitive Functions questionnaire		from baseline at Day 90
Secondary	Change in plasma copeptin and procalcitonin levels		from baseline (Day 1 pre-dose) at Day 90
Secondary	Change in retinal vascular diameter		Day 90 compared to baseline (Day 1 pre-dose)
Secondary	Change in arterial stiffness		Day 90 compared to baseline (Day 1 pre-dose)
Secondary	Change in fractalkine		Day 90 compared to baseline (Day 1 pre-dose)