Type 1 Diabetes MellitusNCT03090451
Exercise Physiology Study
A study testing Aerobic Exercise in people with Type 1 Diabetes Mellitus and Hypoglycemia, run by Oregon Health and Science University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Type 1 Diabetes Mellitus, Hypoglycemia
- What is being tested?
- Aerobic Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2017to 18 Jun 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of type 1 diabetes mellitus for at least 1 year.
- Male or female subjects 18 to 45 years of age.
- Physically willing and able to perform 45 minutes of physical exercise, as determined by the investigator after reviewing the subject's activity level.
- A hemoglobin A1c (HbA1c) less than 10%.
- Willingness to follow all study procedures, including attending all study visits.
- Willingness to sign informed consent and HIPAA documents.
Who cannot join
- 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.
- 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.
- Renal insufficiency (GFR < 60 ml/min, using the MDRD equation as reported by the OHSU laboratory).
- Liver failure, cirrhosis, or any other liver disease that compromises liver function as determined by the investigator.
- Hematocrit of less than 34%.
- 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).
Show all 28Show fewer
- 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.
- Adrenal insufficiency.
- Any active infection.
- Known of suspected abuse of alcohol, narcotics, or illicit drugs.
- Seizure disorder.
- Active foot ulceration.
- Severe peripheral arterial disease characterized by ischemic rest pain or severe claudication.
- Major surgical operation within 30 days prior to screening.
- Use of an investigational drug within 30 days prior to screening.
- Chronic usage of any immunosuppressive medication (such as cyclosporine, azathioprine, sirolimus, or tacrolimus).
- Bleeding disorder, treatment with warfarin, or platelet count below 50,000.
- Insulin resistance requiring more than 200 units per day.
- Current administration of oral or parenteral corticosteroids.
- 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).
- Beta blockers or non-dihydropyridine calcium channel blockers.
- Current use of any medication intended to lower glucose other than insulin (e.g. use of liraglutide, exenatide, etc.)
- Diagnosis of pheochromocytoma, insulinoma, or glucagonoma, personal or family history of multiple endocrine neoplasia (MEN) 2A, MEN 2B, neurofibromatosis or von Hippel-Lindau disease.
- History of severe hypersensitivity to milk protein.
- 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.
- 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.
- Any chest discomfort with physical activity, including pain or pressure, or other types of discomfort.
- Any clinically significant disorder which, in the opinion of the investigator, may jeopardize the subject's safety or compliance with the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: Evaluating the Dynamics of Insulin and Non-insulin Mediated Effects on Glucose During Aerobic Exercise in Subjects With Type 1 Diabetes
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.
Read more
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.
Read the detailed description
Diabetes mellitus afflicts close to 10% of our population and 5% of those with diabetes have type 1, which is defined by an absolute deficiency of insulin. The need for managing diabetes is critical, given the economic burden of this disease, with over $175 billion dollars in direct health care costs, and almost another $70 billion in indirect costs for disability and work loss. The personal impact is equally as important for people with this disease, as diabetes mellitus is the leading cause of blindness, the need for kidney dialysis, and non-traumatic amputations in the United States. Type 2 diabetes is associated with reduced insulin sensitivity and the metabolic syndrome, and dietary modification and exercise are important components in the management of underlying insulin resistance. However, these lifestyle strategies are also important in type 1 diabetes for many reasons: 1) type 1 diabetes subjects now live into adulthood, when insulin resistance and obesity become factors for glycemic control, 2) latent autoimmune diabetes of adulthood (LADA) represents a "mixed" form of autoimmune diabetes where some type 2 diabetes characteristics such as insulin resistance can exist, and 3) dietary modification and exercise remain effective means for management of acute hyperglycemia and, in the longer term, HbA1c, potentially reducing the risk of microvascular complications. Therefore, the need for exercise is still evident in subjects with type 1 diabetes to maintain good glycemic control and to prevent complications from developing. However, exercise is challenging for people with T1D to manage. Exercise causes increased insulin sensitivity along with rapid uptake of glucose by muscle and other tissues within the body, leading to a sharp decline in glucose levels and hypoglycemia as shown by other groups as well as ours.
Without adjustments in insulin for exercise, hypoglycemia is common in persons with type 1 diabetes. In a study of 48 individuals with T1D, with no adjustments to insulin, who exercise for 60 min at a moderate intensity, glucose levels dropped on average by 40%, with 52% of subjects falling to 70 mg/dL or below. Despite this clear need for insulin adjustments for exercise, there are no uniform recommendations on how to dose insulin around the time of exercise. In 2006, the DirecNet Study Group published a study on the impact of suspending basal insulin at the start of exercise in 40 children with type 1 diabetes on insulin pump therapy. This intervention significantly reduced hypoglycemia (from 43% to 16%), but much more commonly resulted in hyperglycemia (increased from 4% to 23%). Schiavon and Cobelli et al addressed this issue of how to best adjust insulin for exercise using in silico simulations. Adjusting insulin doses in the in silico environment decreased hypoglycemia from 88% to 16% of patients when a universal adjustment was applied, and to 4% when an individual adjustment was applied.
The study described within this protocol is designed to disambiguate the impact of exercise on insulin and non-insulin mediated effects on glycemic control. To achieve this, the investigators will perform a series of stable glucose tracer studies in which subjects will be fasting for about 8 hours and will undergo aerobic exercise at a moderate and intense level for 45 minutes while insulin rates are clamped at a low (subject's basal rate), medium (basal x 1.5), and high (basal x 3) insulin infusion rate. Subject's basal rates will be obtained from injected basal insulin amounts, such as NPH/glargine/detemir, or basal rates in those who use insulin pumps and will be adjusted for the HbA1c, as described in the OHSU AP system. Di-deuterated glucose (6,6-2H2-glucose) which is not radioactive and which can be metabolized via usual pathways in the human body will be the stable tracer. Each subject per arm will undergo 3 10-hour studies while blood glucose, insulin, and glucagon levels are captured throughout the study, and catecholamine and fatty acid levels are captured during and just after the exercise period, as outlined below. Glucose tracer levels will be measured at OHSU through the Bioanalytical Shared Resource/PK core lab, and calculation of rate of appearance (Ra) and rate of disappearance (Rd) of glucose will be performed by our colleagues at McGill University using a non-steady state model of glucose dynamics.
The data obtained from this study will inform an updated model of glucose regulation in type 1 diabetes, providing exercise as an input to the model, which will be utilized in a model predictive control (MPC) system for managing type 1 diabetes. Such a system can be used to deliver insulin and/or glucagon to manage glycemic changes during and outside of exercise.
- Conditions
- Type 1 Diabetes Mellitus, Hypoglycemia
- Being tested
- Aerobic Exercise
- Keywords
- Insulin, Glucose Clamp, Glucose Tracer, Artificial Pancreas, Exercise, Aerobic
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia, Insulin Resistance, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aerobic ExerciseBehavioural
Aerobic physical exercise on treadmill, with intensity based on prior VO2-max testing during the screening visit.
| Study group | Role | What they receive |
|---|---|---|
| Moderate Aerobic Exercise | Experimental | 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. Receives: Behavioral: Aerobic Exercise |
| Intense Aerobic Exercise | Experimental | 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. Receives: Behavioral: Aerobic Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-insulin mediated glucose uptake (NIMGU)
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.
Measured: At baselin and at 30 minutes into physical exercise
Secondary outcomes (5)
Insulin mediated glucose uptake (IMGU)
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.
Measured: At baseline and at 30 minutes into physical exercise
Mean glucose level
Mean glucose level throughout the study (without the run-in period)
Measured: 9 hours
Time spent in severe hypoglycemia
Time in minutes spent in the range of glucose < 50 mg/dl.
Measured: 9 hours
Time spent in hypoglycemia
Time in minutes spent in the range of glucose < 70 mg/dl.
Measured: 9 hours
Time spent in hyperglycemia
Time in minutes spent in the range of glucose > 180 mg/dl.
Measured: 9 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2017
- Study start1 May 2017
- Primary completion14 Dec 2018
- Study completion18 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph El Youssef, Oregon Health and Science University
- Investigators
- Joseph El Youssef, MD, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03090451
- Sponsor's protocol ID
- 16761
- Status last verified
- Aug 2019
- First submitted
- 7 Mar 2017
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013 Apr;36(4):1033-46. doi: 10.2337/dc12-2625. Epub 2013 Mar 6.
PubMed 23468086Livingstone SJ, Levin D, Looker HC, Lindsay RS, Wild SH, Joss N, Leese G, Leslie P, McCrimmon RJ, Metcalfe W, McKnight JA, Morris AD, Pearson DW, Petrie JR, Philip S, Sattar NA, Traynor JP, Colhoun HM; Scottish Diabetes Research Network epidemiology group; Scottish Renal Registry. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA. 2015 Jan 6;313(1):37-44. doi: 10.1001/jama.2014.16425.
PubMed 25562264Rusavy Z, Lacigova S. [Life expectancy of people with type 1 diabetes in the past and today]. Vnitr Lek. 2014 Sep;60(9):765-71. Czech.
PubMed 25294766Naik RG, Brooks-Worrell BM, Palmer JP. Latent autoimmune diabetes in adults. J Clin Endocrinol Metab. 2009 Dec;94(12):4635-44. doi: 10.1210/jc.2009-1120. Epub 2009 Oct 16.
PubMed 19837918Yardley JE, Hay J, Abou-Setta AM, Marks SD, McGavock J. A systematic review and meta-analysis of exercise interventions in adults with type 1 diabetes. Diabetes Res Clin Pract. 2014 Dec;106(3):393-400. doi: 10.1016/j.diabres.2014.09.038. Epub 2014 Oct 7.
PubMed 25451913Quirk H, Blake H, Tennyson R, Randell TL, Glazebrook C. Physical activity interventions in children and young people with Type 1 diabetes mellitus: a systematic review with meta-analysis. Diabet Med. 2014 Oct;31(10):1163-73. doi: 10.1111/dme.12531.
PubMed 24965376Breton MD, Brown SA, Karvetski CH, Kollar L, Topchyan KA, Anderson SM, Kovatchev BP. Adding heart rate signal to a control-to-range artificial pancreas system improves the protection against hypoglycemia during exercise in type 1 diabetes. Diabetes Technol Ther. 2014 Aug;16(8):506-11. doi: 10.1089/dia.2013.0333. Epub 2014 Apr 4.
PubMed 24702135Jacobs PG, Resalat N, El Youssef J, Reddy R, Branigan D, Preiser N, Condon J, Castle J. Incorporating an Exercise Detection, Grading, and Hormone Dosing Algorithm Into the Artificial Pancreas Using Accelerometry and Heart Rate. J Diabetes Sci Technol. 2015 Oct 5;9(6):1175-84. doi: 10.1177/1932296815609371.
PubMed 26438720Tansey MJ, Tsalikian E, Beck RW, Mauras N, Buckingham BA, Weinzimer SA, Janz KF, Kollman C, Xing D, Ruedy KJ, Steffes MW, Borland TM, Singh RJ, Tamborlane WV; Diabetes Research in Children Network (DirecNet) Study Group. The effects of aerobic exercise on glucose and counterregulatory hormone concentrations in children with type 1 diabetes. Diabetes Care. 2006 Jan;29(1):20-5. doi: 10.2337/diacare.29.1.20.
PubMed 16373890Diabetes Research in Children Network (DirecNet) Study Group; Tsalikian E, Kollman C, Tamborlane WB, Beck RW, Fiallo-Scharer R, Fox L, Janz KF, Ruedy KJ, Wilson D, Xing D, Weinzimer SA. Prevention of hypoglycemia during exercise in children with type 1 diabetes by suspending basal insulin. Diabetes Care. 2006 Oct;29(10):2200-4. doi: 10.2337/dc06-0495.
PubMed 17003293Schiavon M, Dalla Man C, Kudva YC, Basu A, Cobelli C. In silico optimization of basal insulin infusion rate during exercise: implication for artificial pancreas. J Diabetes Sci Technol. 2013 Nov 1;7(6):1461-9. doi: 10.1177/193229681300700606.
PubMed 24351172Jacobs PG, El Youssef J, Castle JR, Engle JM, Branigan DL, Johnson P, Massoud R, Kamath A, Ward WK. Development of a fully automated closed loop artificial pancreas control system with dual pump delivery of insulin and glucagon. Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:397-400. doi: 10.1109/IEMBS.2011.6090127.
PubMed 22254332Nguyen TP, Jacobs PG, Castle JR, Wilson LM, Kuehl K, Branigan D, Gabo V, Guillot F, Riddell MC, Haidar A, El Youssef J. Separating insulin-mediated and non-insulin-mediated glucose uptake during and after aerobic exercise in type 1 diabetes. Am J Physiol Endocrinol Metab. 2021 Mar 1;320(3):E425-E437. doi: 10.1152/ajpendo.00534.2020. Epub 2020 Dec 28.
PubMed 33356994
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Dynamics of Insulin and Non-insulin Mediated Effects on Glucose During Aerobic Exercise in Subjects With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03090451
- Acronym / sponsor ID
- 16761
- Conditions
- Type 1 Diabetes Mellitus, Hypoglycemia
- Keywords
- Insulin, Glucose Clamp, Glucose Tracer, Artificial Pancreas, Exercise, Aerobic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Study start
- 1 May 2017 (actual)
- Primary completion
- 14 Dec 2018 (actual)
- Study completion
- 18 Jun 2019 (actual)
- First posted
- 24 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Diabetes mellitus afflicts close to 10% of our population and 5% of those with diabetes have type 1, which is defined by an absolute deficiency of insulin. The need for managing diabetes is critical, given the economic burden of this disease, with over $175 billion dollars in direct health care costs, and almost another $70 billion in indirect costs for disability and work loss. The personal impact is equally as important for people with this disease, as diabetes mellitus is the leading cause of blindness, the need for kidney dialysis, and non-traumatic amputations in the United States. Type 2 diabetes is associated with reduced insulin sensitivity and the metabolic syndrome, and dietary modification and exercise are important components in the management of underlying insulin resistance. However, these lifestyle strategies are also important in type 1 diabetes for many reasons: 1) type 1 diabetes subjects now live into adulthood, when insulin resistance and obesity become factors for glycemic control, 2) latent autoimmune diabetes of adulthood (LADA) represents a "mixed" form of autoimmune diabetes where some type 2 diabetes characteristics such as insulin resistance can exist, and 3) dietary modification and exercise remain effective means for management of acute hyperglycemia and, in the longer term, HbA1c, potentially reducing the risk of microvascular complications. Therefore, the need for exercise is still evident in subjects with type 1 diabetes to maintain good glycemic control and to prevent complications from developing. However, exercise is challenging for people with T1D to manage. Exercise causes increased insulin sensitivity along with rapid uptake of glucose by muscle and other tissues within the body, leading to a sharp decline in glucose levels and hypoglycemia as shown by other groups as well as ours.
Without adjustments in insulin for exercise, hypoglycemia is common in persons with type 1 diabetes. In a study of 48 individuals with T1D, with no adjustments to insulin, who exercise for 60 min at a moderate intensity, glucose levels dropped on average by 40%, with 52% of subjects falling to 70 mg/dL or below. Despite this clear need for insulin adjustments for exercise, there are no uniform recommendations on how to dose insulin around the time of exercise. In 2006, the DirecNet Study Group published a study on the impact of suspending basal insulin at the start of exercise in 40 children with type 1 diabetes on insulin pump therapy. This intervention significantly reduced hypoglycemia (from 43% to 16%), but much more commonly resulted in hyperglycemia (increased from 4% to 23%). Schiavon and Cobelli et al addressed this issue of how to best adjust insulin for exercise using in silico simulations. Adjusting insulin doses in the in silico environment decreased hypoglycemia from 88% to 16% of patients when a universal adjustment was applied, and to 4% when an individual adjustment was applied.
The study described within this protocol is designed to disambiguate the impact of exercise on insulin and non-insulin mediated effects on glycemic control. To achieve this, the investigators will perform a series of stable glucose tracer studies in which subjects will be fasting for about 8 hours and will undergo aerobic exercise at a moderate and intense level for 45 minutes while insulin rates are clamped at a low (subject's basal rate), medium (basal x 1.5), and high (basal x 3) insulin infusion rate. Subject's basal rates will be obtained from injected basal insulin amounts, such as NPH/glargine/detemir, or basal rates in those who use insulin pumps and will be adjusted for the HbA1c, as described in the OHSU AP system. Di-deuterated glucose (6,6-2H2-glucose) which is not radioactive and which can be metabolized via usual pathways in the human body will be the stable tracer. Each subject per arm will undergo 3 10-hour studies while blood glucose, insulin, and glucagon levels are captured throughout the study, and catecholamine and fatty acid levels are captured during and just after the exercise period, as outlined below. Glucose tracer levels will be measured at OHSU through the Bioanalytical Shared Resource/PK core lab, and calculation of rate of appearance (Ra) and rate of disappearance (Rd) of glucose will be performed by our colleagues at McGill University using a non-steady state model of glucose dynamics.
The data obtained from this study will inform an updated model of glucose regulation in type 1 diabetes, providing exercise as an input to the model, which will be utilized in a model predictive control (MPC) system for managing type 1 diabetes. Such a system can be used to deliver insulin and/or glucagon to manage glycemic changes during and outside of exercise.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Moderate Aerobic Exercise | Experimental | Behavioral: Aerobic ExerciseSubjects 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. |
| Intense Aerobic Exercise | Experimental | Behavioral: Aerobic ExerciseSubjects 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Diagnosis of type 1 diabetes mellitus for at least 1 year.
- Male or female subjects 18 to 45 years of age.
- Physically willing and able to perform 45 minutes of physical exercise, as determined by the investigator after reviewing the subject's activity level.
- A hemoglobin A1c (HbA1c) less than 10%.
- Willingness to follow all study procedures, including attending all study visits.
Key exclusion criteria (28 listed)
- 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.
- 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.
- Renal insufficiency (GFR < 60 ml/min, using the MDRD equation as reported by the OHSU laboratory).
- Liver failure, cirrhosis, or any other liver disease that compromises liver function as determined by the investigator.
- Hematocrit of less than 34%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aerobic ExerciseAerobic physical exercise on treadmill, with intensity based on prior VO2-max testing during the screening visit. | Behavioural | Intense Aerobic Exercise, Moderate Aerobic Exercise |
Primary outcome
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.
5 secondary outcomes
Insulin mediated glucose uptake (IMGU)
Time frame: At baseline and at 30 minutes into physical exercise
Mean glucose level
Time frame: 9 hours
Time spent in severe hypoglycemia
Time frame: 9 hours
Time spent in hypoglycemia
Time frame: 9 hours
Time spent in hyperglycemia
Time frame: 9 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Background: PubMed 23468086American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013 Apr;36(4):1033-46. doi: 10.2337/dc12-2625. Epub 2013 Mar 6.
- Background: PubMed 25562264Livingstone SJ, Levin D, Looker HC, Lindsay RS, Wild SH, Joss N, Leese G, Leslie P, McCrimmon RJ, Metcalfe W, McKnight JA, Morris AD, Pearson DW, Petrie JR, Philip S, Sattar NA, Traynor JP, Colhoun HM; Scottish Diabetes Research Network epidemiology group; Scottish Renal Registry. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA. 2015 Jan 6;313(1):37-44. doi: 10.1001/jama.2014.16425.
- Background: PubMed 25294766Rusavy Z, Lacigova S. [Life expectancy of people with type 1 diabetes in the past and today]. Vnitr Lek. 2014 Sep;60(9):765-71. Czech.
- Background: PubMed 19837918Naik RG, Brooks-Worrell BM, Palmer JP. Latent autoimmune diabetes in adults. J Clin Endocrinol Metab. 2009 Dec;94(12):4635-44. doi: 10.1210/jc.2009-1120. Epub 2009 Oct 16.
- Background: PubMed 25451913Yardley JE, Hay J, Abou-Setta AM, Marks SD, McGavock J. A systematic review and meta-analysis of exercise interventions in adults with type 1 diabetes. Diabetes Res Clin Pract. 2014 Dec;106(3):393-400. doi: 10.1016/j.diabres.2014.09.038. Epub 2014 Oct 7.
- Background: PubMed 24965376Quirk H, Blake H, Tennyson R, Randell TL, Glazebrook C. Physical activity interventions in children and young people with Type 1 diabetes mellitus: a systematic review with meta-analysis. Diabet Med. 2014 Oct;31(10):1163-73. doi: 10.1111/dme.12531.
- Background: PubMed 24702135Breton MD, Brown SA, Karvetski CH, Kollar L, Topchyan KA, Anderson SM, Kovatchev BP. Adding heart rate signal to a control-to-range artificial pancreas system improves the protection against hypoglycemia during exercise in type 1 diabetes. Diabetes Technol Ther. 2014 Aug;16(8):506-11. doi: 10.1089/dia.2013.0333. Epub 2014 Apr 4.
- Background: PubMed 26438720Jacobs PG, Resalat N, El Youssef J, Reddy R, Branigan D, Preiser N, Condon J, Castle J. Incorporating an Exercise Detection, Grading, and Hormone Dosing Algorithm Into the Artificial Pancreas Using Accelerometry and Heart Rate. J Diabetes Sci Technol. 2015 Oct 5;9(6):1175-84. doi: 10.1177/1932296815609371.
- Background: PubMed 16373890Tansey MJ, Tsalikian E, Beck RW, Mauras N, Buckingham BA, Weinzimer SA, Janz KF, Kollman C, Xing D, Ruedy KJ, Steffes MW, Borland TM, Singh RJ, Tamborlane WV; Diabetes Research in Children Network (DirecNet) Study Group. The effects of aerobic exercise on glucose and counterregulatory hormone concentrations in children with type 1 diabetes. Diabetes Care. 2006 Jan;29(1):20-5. doi: 10.2337/diacare.29.1.20.
- Background: PubMed 17003293Diabetes Research in Children Network (DirecNet) Study Group; Tsalikian E, Kollman C, Tamborlane WB, Beck RW, Fiallo-Scharer R, Fox L, Janz KF, Ruedy KJ, Wilson D, Xing D, Weinzimer SA. Prevention of hypoglycemia during exercise in children with type 1 diabetes by suspending basal insulin. Diabetes Care. 2006 Oct;29(10):2200-4. doi: 10.2337/dc06-0495.
- Background: PubMed 24351172Schiavon M, Dalla Man C, Kudva YC, Basu A, Cobelli C. In silico optimization of basal insulin infusion rate during exercise: implication for artificial pancreas. J Diabetes Sci Technol. 2013 Nov 1;7(6):1461-9. doi: 10.1177/193229681300700606.
- Background: PubMed 22254332Jacobs PG, El Youssef J, Castle JR, Engle JM, Branigan DL, Johnson P, Massoud R, Kamath A, Ward WK. Development of a fully automated closed loop artificial pancreas control system with dual pump delivery of insulin and glucagon. Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:397-400. doi: 10.1109/IEMBS.2011.6090127.
- Individual participant dataSharing planned: No
Related trials for Type 1 Diabetes Mellitus
Recruiting
Clinical Study to Evaluate the Impact of the Accu-Chek SmartGuide CGM Solution on the Mean Change in Time in Range Compared With Self-Monitoring of Blood Glucose in Participants With Type 1 and Type 2 Diabetes Mellitus
Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
Active, not recruitingPhase 2
Islet Cell Transplant for Type 1 Diabetes
Type 1 Diabetes Mellitus
Recruiting
T1CARE: A Trial of a Novel Intervention to Address Social Determinants of Health in Young Adults With Type 1 Diabetes
Type 1 Diabetes
Active, not recruitingPhase 4
Diabetes in African Youth
type1diabetes
RecruitingObservational study
Washed Microbiota Transplantation for Type 1 Diabetes Mellitus
Type 1 Diabetes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph El Youssef, MD principal investigator
Oregon Health and Science University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aerobic Exercise in people with Type 1 Diabetes Mellitus and Hypoglycemia, run by Oregon Health and Science University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-insulin mediated glucose uptake (NIMGU) (time frame: At baselin and at 30 minutes into physical exercise). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03090451, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.