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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University Hospital, Basel, Switzerland
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT02127047
First received: April 28, 2014
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus Type 1
Drug: Sitagliptin
Drug: Exercise
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Exercise and Inhibition of Dipeptidyl Peptidase-4 on Insulin Secretion in Subjects With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Change in HbA1c levels [ Time Frame: baseline (Day 1 pre-dose) at Day 90 ] [ Designated as safety issue: No ]
  • Change in fasting glucose [ Time Frame: baseline (Day 1 pre-dose) at Day 90 ] [ Designated as safety issue: No ]
  • Change in fasting glucagon and cortisol [ Time Frame: baseline (Day 1 pre-dose) at Day 90 ] [ Designated as safety issue: No ]
  • Change in total number of hypoglycemic events compared to treatment groups [ Time Frame: baseline (Day 1 pre-dose) to Day 90 ] [ Designated as safety issue: No ]
  • Change in markers of systemic inflammation [ Time Frame: from baseline (Day 1 pre-dose) at Day 90 ] [ Designated as safety issue: No ]
  • Change in composition of immune cells [ Time Frame: from baseline at Day 90 ] [ Designated as safety issue: No ]
  • Change in meal-stimulated GLP-1 and gastric inhibitory peptide [ Time Frame: Day 90 compared to baseline ] [ Designated as safety issue: No ]
  • Change in lipids profile [ Time Frame: baseline at Day 90 ] [ Designated as safety issue: No ]
  • Change in fatigue according to the Fatigue Scale for Motor and Cognitive Functions questionnaire [ Time Frame: from baseline at Day 90 ] [ Designated as safety issue: No ]
  • Change in plasma copeptin and procalcitonin levels [ Time Frame: from baseline (Day 1 pre-dose) at Day 90 ] [ Designated as safety issue: No ]
  • Change in retinal vascular diameter [ Time Frame: Day 90 compared to baseline (Day 1 pre-dose) ] [ Designated as safety issue: No ]
  • Change in arterial stiffness [ Time Frame: Day 90 compared to baseline (Day 1 pre-dose) ] [ Designated as safety issue: No ]
  • Change in fractalkine [ Time Frame: Day 90 compared to baseline (Day 1 pre-dose) ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: November 2013
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
Patients receive Sitagliptin (100mg/d) without further intervention
Drug: Sitagliptin
Experimental: Sitagliptin and exercise
Patients receive sitagliptin (100mg/d) and follow a physical training intervention program
Drug: Sitagliptin Drug: Exercise

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02127047

Contacts
Contact: Marc Donath, Principal Investigator 61 265 25 25 ext 0041 marc.donath@usb.ch

Locations
Switzerland
University Hospital Basel Recruiting
Basel, Switzerland, 4031
Contact: Marc Donath       marc.donath@usb.ch   
Principal Investigator: Marc Donath, Prof. Dr.         
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Marc Donath, Prof. MD University Hospital, Basel, Switzerland
  More Information

No publications provided

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT02127047     History of Changes
Other Study ID Numbers: EKBB 349/12
Study First Received: April 28, 2014
Last Updated: April 29, 2014
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Sitagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014