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

Primary Purpose

Diabetes Mellitus Type 1

Status

Completed

Phase

Phase 2

Locations

Switzerland

Study Type

Interventional

Intervention

Sitagliptin

Exercise

About this trial

This is an interventional treatment trial for Diabetes Mellitus Type 1

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

University Hospital Basel

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Sitagliptin

Sitagliptin and exercise

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

Change in HbA1c levels

Change in fasting glucose

Change in fasting glucagon and cortisol

Change in total number of hypoglycemic events compared to treatment groups

Change in markers of systemic inflammation

Change in composition of immune cells

Change in meal-stimulated GLP-1 and gastric inhibitory peptide

Change in lipids profile

Change in fatigue according to the Fatigue Scale for Motor and Cognitive Functions questionnaire

Change in plasma copeptin and procalcitonin levels

Change in retinal vascular diameter

Change in arterial stiffness

Change in fractalkine

Full Information

NCT ID

NCT02127047

First Posted

April 28, 2014

Last Updated

July 25, 2017

Sponsor

University Hospital, Basel, Switzerland

1. Study Identification

Unique Protocol Identification Number

NCT02127047

Brief Title

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

Acronym

EXTYPE-1

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Completed

Study Start Date

November 2013 (undefined)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

August 5, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Basel, Switzerland

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus Type 1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sitagliptin

Arm Type

Experimental

Arm Description

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

Arm Title

Sitagliptin and exercise

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Sitagliptin

Intervention Type

Drug

Intervention Name(s)

Exercise

Primary Outcome Measure Information:

Title

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

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Time Frame

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

Title

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

Time Frame

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

Title

Change in HbA1c levels

Time Frame

baseline (Day 1 pre-dose) at Day 90

Title

Change in fasting glucose

Time Frame

baseline (Day 1 pre-dose) at Day 90

Title

Change in fasting glucagon and cortisol

Time Frame

baseline (Day 1 pre-dose) at Day 90

Title

Change in total number of hypoglycemic events compared to treatment groups

Time Frame

baseline (Day 1 pre-dose) to Day 90

Title

Change in markers of systemic inflammation

Time Frame

from baseline (Day 1 pre-dose) at Day 90

Title

Change in composition of immune cells

Time Frame

from baseline at Day 90

Title

Change in meal-stimulated GLP-1 and gastric inhibitory peptide

Time Frame

Day 90 compared to baseline

Title

Change in lipids profile

Time Frame

baseline at Day 90

Title

Change in fatigue according to the Fatigue Scale for Motor and Cognitive Functions questionnaire

Time Frame

from baseline at Day 90

Title

Change in plasma copeptin and procalcitonin levels

Time Frame

from baseline (Day 1 pre-dose) at Day 90

Title

Change in retinal vascular diameter

Time Frame

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

Title

Change in arterial stiffness

Time Frame

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

Title

Change in fractalkine

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marc Donath, Prof. MD

Organizational Affiliation

University Hospital, Basel, Switzerland

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Basel

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

12. IPD Sharing Statement

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

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