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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02127047
First Posted: April 30, 2014
Last Update Posted: July 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
  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
Intervention Model: Parallel Assignment
Masking: None (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) ]

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

Enrollment: 24
Study Start Date: November 2013
Study Completion Date: August 5, 2016
Primary Completion Date: July 2016 (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

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
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 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02127047


Locations
Switzerland
University Hospital Basel
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Marc Donath, Prof. MD University Hospital, Basel, Switzerland
  More Information

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT02127047     History of Changes
Other Study ID Numbers: EKBB 349/12
First Submitted: April 28, 2014
First Posted: April 30, 2014
Last Update Posted: July 27, 2017
Last Verified: July 2017

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