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Exercise Physiology Study

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ClinicalTrials.gov Identifier: NCT03090451
Recruitment Status : Completed
First Posted : March 24, 2017
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Joseph El Youssef, Oregon Health and Science University

Brief Summary:

People with type 1 diabetes often find exercise very difficult to manage, because of the high risk for low blood glucose levels. This can occur very quickly once exercise starts and presents many risks for subjects, such as severe symptoms, confusion, passing out, seizures, and even coma or death in very severe cases. Preventing low blood glucose levels during and after exercise is important because physical exercise is a key component of managing diabetes. It is often hard to correctly adjust insulin infusion rates or doses before exercise as the relationship between exercise and changes in glucose levels in those who have type 1 diabetes is still not fully understood. Therefore, the investigators propose this study to further our understanding in this area.

This study is designed to help separate the effects of insulin from those of muscle work (non-insulin effects) on the changes in blood glucose levels during aerobic exercise. The main hypothesis is that the non-insulin effects occur quickly during exercise and account for the rapid change in blood glucose levels once aerobic exercise begins. These effects can be separated from the slower changes in insulin sensitivity that occur because of exercise, and which account for reduced insulin demand even after exercise has stopped. The investigators will investigate the effects of both moderate and intense aerobic exercise at different levels of insulin in the body to help separate the insulin and non-insulin effects.

The investigators wish to recruit 26 subjects to take part in this study. Subjects will be randomly divided into two groups, with 13 in each group. Group 1 will undergo moderate aerobic exercise, while group 2 will undergo intense aerobic exercise. Each subject will repeat the exercise study three times on three separate days at least 2 weeks apart, while having insulin infused at a low, a medium, and a high rate. Subjects will have an IV line placed in each arm, one for drawing blood relatively frequently during the study, and another for infusion of insulin, glucose, and a special glucose tracer (non-radioactive). Each study lasts about 9 hours.

Information from this study will be used to help develop a mathematical model of how glucose changes during exercise in type 1 diabetes. Such a model of type 1 diabetes and exercise will be very useful for adjusting insulin doses in patients who use multiple daily injections of insulin, and can help to guide an automated insulin delivery system, such as the artificial pancreas.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Hypoglycemia Behavioral: Aerobic Exercise Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Two main arms: 1) moderate aerobic exercise, 2) intense aerobic exercise. In each arm, subjects will undergo three separate studies, i) at low insulin levels, ii) at medium insulin levels, and iii) at high insulin levels.
Masking: None (Open Label)
Masking Description: No masking for this study.
Primary Purpose: Basic Science
Official Title: Evaluating the Dynamics of Insulin and Non-insulin Mediated Effects on Glucose During Aerobic Exercise in Subjects With Type 1 Diabetes
Actual Study Start Date : May 1, 2017
Actual Primary Completion Date : December 14, 2018
Actual Study Completion Date : December 14, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Moderate Aerobic Exercise
Subjects will undergo moderate aerobic physical exercise (40-45% of VO2-max) on three separate days at i) low insulin levels, ii) medium insulin levels, and iii) high insulin levels.
Behavioral: Aerobic Exercise
Aerobic physical exercise on treadmill, with intensity based on prior VO2-max testing during the screening visit.

Experimental: Intense Aerobic Exercise
Subjects will undergo intense aerobic physical exercise (60-65% of VO2-max) on three separate days at i) low insulin levels, ii) medium insulin levels, and iii) high insulin levels.
Behavioral: Aerobic Exercise
Aerobic physical exercise on treadmill, with intensity based on prior VO2-max testing during the screening visit.




Primary Outcome Measures :
  1. Non-insulin mediated glucose uptake (NIMGU) [ Time Frame: At baselin and at 30 minutes into physical exercise ]
    Rate of disappearance of glucose in [mg/kg]/min during exercise that is not related to the insulin effect, as calculated using a non-steady state model of glucose dynamics. This will be compared to the baseline NIMGU before exercise.


Secondary Outcome Measures :
  1. Insulin mediated glucose uptake (IMGU) [ Time Frame: At baseline and at 30 minutes into physical exercise ]
    Rate of disappearance of glucose in [mg/kg]/min during exercise that is related to the insulin effect, as calculated using a non-steady state model of glucose dynamics.This will be compared to the baseline IMGU before exercise.

  2. Mean glucose level [ Time Frame: 9 hours ]
    Mean glucose level throughout the study (without the run-in period)

  3. Time spent in severe hypoglycemia [ Time Frame: 9 hours ]
    Time in minutes spent in the range of glucose < 50 mg/dl.

  4. Time spent in hypoglycemia [ Time Frame: 9 hours ]
    Time in minutes spent in the range of glucose < 70 mg/dl.

  5. Time spent in hyperglycemia [ Time Frame: 9 hours ]
    Time in minutes spent in the range of glucose > 180 mg/dl.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of type 1 diabetes mellitus for at least 1 year.
  2. Male or female subjects 18 to 45 years of age.
  3. Physically willing and able to perform 45 minutes of physical exercise, as determined by the investigator after reviewing the subject's activity level.
  4. A hemoglobin A1c (HbA1c) less than 10%.
  5. Willingness to follow all study procedures, including attending all study visits.
  6. Willingness to sign informed consent and HIPAA documents.

Exclusion Criteria:

  1. Female of childbearing potential who is pregnant, intending to become pregnant, breast-feeding, or is not using adequate contraceptive methods. Acceptable contraception includes birth control pill/patch/vaginal ring, Depo-Provera, Norplant, an IUD, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
  2. Any cardiovascular disease, defined as clinically significant EKG abnormality at the time of screening, or any history of: stroke, heart failure, myocardial infarction, angina pectoris, coronary arterial bypass grafting, or angioplasty. Diagnosis of 2nd or 3rd degree heart block or any non-physiological arrhythmia may be judged by the investigator to be exclusionary.
  3. Renal insufficiency (GFR < 60 ml/min, using the MDRD equation as reported by the OHSU laboratory).
  4. Liver failure, cirrhosis, or any other liver disease that compromises liver function as determined by the investigator.
  5. Hematocrit of less than 34%.
  6. Hypertension with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg despite treatment or who have treatment-refractory hypertension (e.g. requiring four or more medications).
  7. History of severe hypoglycemia during the past 12 months prior to screening visit or hypoglycemia unawareness as judged by the investigator. Subjects will complete a hypoglycemia awareness questionnaire (included in Appendix A). Subjects will be excluded for four or more 'R' responses.
  8. Adrenal insufficiency.
  9. Any active infection.
  10. Known of suspected abuse of alcohol, narcotics, or illicit drugs.
  11. Seizure disorder.
  12. Active foot ulceration.
  13. Severe peripheral arterial disease characterized by ischemic rest pain or severe claudication.
  14. Major surgical operation within 30 days prior to screening.
  15. Use of an investigational drug within 30 days prior to screening.
  16. Chronic usage of any immunosuppressive medication (such as cyclosporine, azathioprine, sirolimus, or tacrolimus).
  17. Bleeding disorder, treatment with warfarin, or platelet count below 50,000.
  18. Insulin resistance requiring more than 200 units per day.
  19. Current administration of oral or parenteral corticosteroids.
  20. Any life-threatening disease, including malignant neoplasms and medical history of malignant neoplasms within the past 5 years prior to screening (except basal cell cancer of the skin).
  21. Beta blockers or non-dihydropyridine calcium channel blockers.
  22. Current use of any medication intended to lower glucose other than insulin (e.g. use of liraglutide, exenatide, etc.)
  23. Diagnosis of pheochromocytoma, insulinoma, or glucagonoma, personal or family history of multiple endocrine neoplasia (MEN) 2A, MEN 2B, neurofibromatosis or von Hippel-Lindau disease.
  24. History of severe hypersensitivity to milk protein.
  25. Conditions that may result in low levels of releasable glucose in the liver and an inadequate reversal of hypoglycemia by glucagon such as prolonged fasting, starvation or chronic hypoglycemia as determined by the investigator.
  26. A positive response to any of the questions from the Physical Activity Readiness Questionnaire with one exception: subject will not be excluded if only a single blood pressure medication that doesn't impact heart rate is used, and blood pressure is controlled on the medication (blood pressure is less than 140/90 mmHg). See Appendix B.
  27. Any chest discomfort with physical activity, including pain or pressure, or other types of discomfort.
  28. Any clinically significant disorder which, in the opinion of the investigator, may jeopardize the subject's safety or compliance with the protocol.

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): NCT03090451


Locations
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United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Investigators
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Principal Investigator: Joseph El Youssef, MD Oregon Health and Science University

Publications:

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Responsible Party: Joseph El Youssef, Assistant Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT03090451     History of Changes
Other Study ID Numbers: 16761
First Posted: March 24, 2017    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Joseph El Youssef, Oregon Health and Science University:
Insulin
Glucose Clamp
Glucose Tracer
Artificial Pancreas
Exercise
Aerobic

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs