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Influence of Endothelial Function on Central and Peripheral Causes Of Exercise Impairment in Type 2 Diabetes (InsITE)

Primary Purpose

Type 2 Diabetes

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exercise program
Ascorbic Acid (Vitamin C)
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Type 2 Diabetes focused on measuring Type, 2, Diabetes, Blood, Vessel, Function, Exercise, Program, Intervention, Vitamin, C, Men, Women, Blood vessel function

Eligibility Criteria

30 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Men and women with uncomplicated Type 2 Diabetes
  • Healthy men and women without Type 2 Diabetes
  • Patients with Type 2 Diabetes may be taking metformin or sulfonylurea drugs to treat diabetes
  • Persons with history of hypercholesteremia if controlled with statins and/or diet
  • Patients who are moderately overweight (BMI 25-37.5)
  • Must be sedentary (defined as regular exercise < 2 times a week at a low to moderate level).
  • Patients with Hemoglobin A1c (HBA1C) <8%
  • Patients between the ages of 30 to 55 years
  • Premenopausal women.
  • Former smokers who have quit smoking for at least one year
  • Absence of comorbid conditions
  • Mild neuropathy is O.K. as long as it will not hamper exercise performance.
  • Resting systolic blood pressure (SBP) < 140, Resting diastolic blood pressure (DBP) < 90
  • Total Cholesterol < 205 Triglycerides < 250 low density lipoprotein (LDL) < 130
  • Control subjects with a normal A1C and fasting glucose

Exclusion Criteria:

  • People with T2DM taking oral medications, other than metformin or sulfonylurea drugs to control their diabetes.
  • Persons treated with insulin will be excluded
  • People who are currently smoking or have not quit for at least one year
  • Controls who have immediate family history of T2DM
  • Peri-menopausal or post-menopausal women.
  • Peripheral neuropathy
  • Total cholesterol > 205
  • Regional wall motion abnormalities
  • LV wall thickness ≥1.1 cm
  • Decreased contractility (fractional shortening <30%)
  • Ischemic heart disease (abnormal resting or exercise ECG)
  • Presence of angina that would limit exercise performance
  • Pulmonary problems that would limit exercise performance
  • Systolic blood pressure >140 mmHg at rest or >250 mmHg with exercise or diastolic pressure >90 mmHg at rest or >105 mmHg with exercise
  • Persons with autonomic insufficiency, assessed by measuring variation in RR intervals with cycled breathing and by presence of a >20 mm fall in upright blood pressure without a change in heart rate
  • Proteinuria (urine protein >200 mg/dl) or a creatinine > 2 mg/dl
  • Renal disease

Sites / Locations

  • University of Colorado Denver

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ascorbic acid

Arm Description

All study subjects have ascorbic acid infusion during one exercise visit as well as a three month exercise training intervention.

Outcomes

Primary Outcome Measures

Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training
Characterize the purported cardiac dysfunction during exercise in people with type 2 diabetes (T2D). In a normal patient when measuring circumferential strain, results are negative with downward tracing (as strain is a relative change in length). Circumferential strain is a measurement of ventricular circumference within the heart vessels, measured via echocardiography.
Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training
Evaluate potential changes in cardiac function by echocardiography following 2 interventions: Three months of exercise training and acute vitamin C administration. Ejection fraction (EF) is a measurement of the percentage of blood leaving your heart each time it contracts, typically measure by echocardiography. Numbers listed are absolute EF values.

Secondary Outcome Measures

Full Information

First Posted
November 4, 2008
Last Updated
July 10, 2023
Sponsor
University of Colorado, Denver
Collaborators
American Diabetes Association, National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT00786019
Brief Title
Influence of Endothelial Function on Central and Peripheral Causes Of Exercise Impairment in Type 2 Diabetes
Acronym
InsITE
Official Title
Influence Of Endothelial Function On Central and Peripheral Causes Of Exercise Impairment In Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
American Diabetes Association, National Institutes of Health (NIH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will evaluate the effects of impaired blood flow regulation on exercise. It will also determine whether the effects are more important in the heart or in the skeletal muscle tissue during exercise. In addition, this study will decide whether temporarily reversing these problems will improve blood flow control, improve heart and muscle tissue function and help improve exercise capacity in person with type 2 diabetes. This study will do so using two methods: (1) by giving vitamin C intravenously (IV) and (2) a three month exercise training program. Up to 100 subjects will be enrolled in this study.
Detailed Description
The investigators have found that persons with type 2 diabetes have an impaired ability to perform exercise even without clinically apparent complications. The reasons for this marked abnormality are unknown but are important as the decreased ability to exercise could contribute to the decreased expenditure of physical activity frequently observed in this population and may potentially constitute an early marker of cardiovascular disease. The investigators wish to evaluate the effects of impaired blood flow regulation on exercise capacity and whether the effects are more important in the heart or in the skeletal muscle tissue during exercise. In addition, the investigators are determining whether correcting these abnormalities by two methods of improving blood flow regulation (acutely infusing Vitamin C or three months of chronic exercise training) leads to improved blood flow regulation, improved heart and skeletal muscle tissue function and hence to better exercise capacity in person with type 2 diabetes. This information will provide a more mechanistic understanding of causes of abnormal exercise responses observed in person with type 2 diabetes as well as whether and to what degree responses are modifiable. Interventions that reverse the exercise defect may facilitate patient adherence to prescribed physical activity programs and potentially decrease cardiovascular mortality in this large segment of the population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes
Keywords
Type, 2, Diabetes, Blood, Vessel, Function, Exercise, Program, Intervention, Vitamin, C, Men, Women, Blood vessel function

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ascorbic acid
Arm Type
Experimental
Arm Description
All study subjects have ascorbic acid infusion during one exercise visit as well as a three month exercise training intervention.
Intervention Type
Behavioral
Intervention Name(s)
Exercise program
Other Intervention Name(s)
Exercise Training
Intervention Description
Three month exercise program located at the Anschutz Medical Campus at I-225 and Colfax. The program runs three times per week for about an hour each session. Gym is open Monday - Saturday during specific hours (morning, noon, evening).
Intervention Type
Drug
Intervention Name(s)
Ascorbic Acid (Vitamin C)
Other Intervention Name(s)
Ascorbic Acid, Vitamin C
Intervention Description
During one exercise study visit, 0.06 grams of Vitamin C per kilogram fat-free mass per 100 milliliters (mL) of normal saline administered; Subjects will receive a bolus of 100mL Vitamin C solution given at 5ml/minute over 20 minutes followed by a "drip-infusion" given at 1.7ml/minute.
Primary Outcome Measure Information:
Title
Percent Change in Circumferential Strain Before and After Exercise at Baseline, After Vitamin C Infusion, and After Exercise Training
Description
Characterize the purported cardiac dysfunction during exercise in people with type 2 diabetes (T2D). In a normal patient when measuring circumferential strain, results are negative with downward tracing (as strain is a relative change in length). Circumferential strain is a measurement of ventricular circumference within the heart vessels, measured via echocardiography.
Time Frame
7 months; Measures are made at rest and after exercise for baseline, at rest and after infusion for Vitamin C administration, and at rest and after exercise following the exercise training
Title
Ejection Fraction: Percentage of Blood Leaving the Heart Before and After Exercise at Baseline, After a Vitamin C Infusion, and After Exercise Training
Description
Evaluate potential changes in cardiac function by echocardiography following 2 interventions: Three months of exercise training and acute vitamin C administration. Ejection fraction (EF) is a measurement of the percentage of blood leaving your heart each time it contracts, typically measure by echocardiography. Numbers listed are absolute EF values.
Time Frame
7 months; Measures are made at rest for baseline, at rest for Vitamin C administration, and at rest following the exercise training

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Men and women with uncomplicated Type 2 Diabetes Healthy men and women without Type 2 Diabetes Patients with Type 2 Diabetes may be taking metformin or sulfonylurea drugs to treat diabetes Persons with history of hypercholesteremia if controlled with statins and/or diet Patients who are moderately overweight (BMI 25-37.5) Must be sedentary (defined as regular exercise < 2 times a week at a low to moderate level). Patients with Hemoglobin A1c (HBA1C) <8% Patients between the ages of 30 to 55 years Premenopausal women. Former smokers who have quit smoking for at least one year Absence of comorbid conditions Mild neuropathy is O.K. as long as it will not hamper exercise performance. Resting systolic blood pressure (SBP) < 140, Resting diastolic blood pressure (DBP) < 90 Total Cholesterol < 205 Triglycerides < 250 low density lipoprotein (LDL) < 130 Control subjects with a normal A1C and fasting glucose Exclusion Criteria: People with T2DM taking oral medications, other than metformin or sulfonylurea drugs to control their diabetes. Persons treated with insulin will be excluded People who are currently smoking or have not quit for at least one year Controls who have immediate family history of T2DM Peri-menopausal or post-menopausal women. Peripheral neuropathy Total cholesterol > 205 Regional wall motion abnormalities LV wall thickness ≥1.1 cm Decreased contractility (fractional shortening <30%) Ischemic heart disease (abnormal resting or exercise ECG) Presence of angina that would limit exercise performance Pulmonary problems that would limit exercise performance Systolic blood pressure >140 mmHg at rest or >250 mmHg with exercise or diastolic pressure >90 mmHg at rest or >105 mmHg with exercise Persons with autonomic insufficiency, assessed by measuring variation in RR intervals with cycled breathing and by presence of a >20 mm fall in upright blood pressure without a change in heart rate Proteinuria (urine protein >200 mg/dl) or a creatinine > 2 mg/dl Renal disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith G Regensteiner, PhD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29456629
Citation
Scalzo RL, Bauer TA, Harrall K, Moreau K, Ozemek C, Herlache L, McMillin S, Huebschmann AG, Dorosz J, Reusch JEB, Regensteiner JG. Acute vitamin C improves cardiac function, not exercise capacity, in adults with type 2 diabetes. Diabetol Metab Syndr. 2018 Feb 14;10:7. doi: 10.1186/s13098-018-0306-9. eCollection 2018.
Results Reference
derived

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Influence of Endothelial Function on Central and Peripheral Causes Of Exercise Impairment in Type 2 Diabetes

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