Comparing Long-acting Insulins During Exercise in Type 1 Diabetes

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by Buckinghamshire Healthcare NHS Trust.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Buckinghamshire Healthcare NHS Trust
ClinicalTrials.gov Identifier:
NCT01440439
First received: September 20, 2011
Last updated: November 7, 2011
Last verified: November 2011
  Purpose

Exercise is an important part of a healthy lifestyle, and many people with Type 1 Diabetes like to take part in regular sport and exercise. The majority of people with Type 1 Diabetes are treated with a "basal bolus" insulin regimen, with background insulin provided by long-acting "basal" insulin doses, and "bolus" doses of short-acting insulin used to accompany food intake. Evidence shows that the main factor preventing people with diabetes from pursuing a more active lifestyle is fear of low blood glucose (hypoglycaemia). A previous study has shown that the type of background insulin affects the likelihood of an individual suffering hypoglycaemia during exercise and for 2 and a half hours afterwards. The aim of this study is to examine this further.

The two most commonly used long-acting insulins, insulin glargine and insulin detemir, will be compared. Previous data suggests that there is a greater likelihood of hypoglycaemia with insulin glargine than insulin detemir. Exercise intensity can have an influence on the likelihood of hypoglycaemia, and in this previous study exercise intensity was measured using heart rate. This study will use a more formal definition of exercise intensity. The investigators will study blood glucose during exercise, but also metabolism as measured by hormones affecting blood glucose levels as well as markers of fat metabolism. The investigators will also use a continuous glucose monitoring system (CGMS) to consider hypoglycaemia on thei night following exercise as this is a recognised consequence of exercise in type 1 diabetes.

The null hypothesis to be tested in this study is that there is no difference between the two insulins in their effect on blood glucose levels and metabolism during exercise and rates of nocturnal hypoglycaemia after exercise.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: Insulin glargine
Drug: Insulin detemir
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Impact of Insulin Detemir Versus Insulin Glargine on Glycaemic Control and Metabolism During Exercise in Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Buckinghamshire Healthcare NHS Trust:

Primary Outcome Measures:
  • Glucose excursion (which, as defined below, is the change in blood glucose between the start and finish of one hour of exercise) [ Time Frame: Between baseline and 1 hour ] [ Designated as safety issue: No ]
    The measure will be a comparison between the two conditions (treatment with insulin detemir or treatment with insulin glargine) of the change in blood glucose levels during one hour of sub-maximal exercise at 50% VO2 MAX


Secondary Outcome Measures:
  • Lactate [ Time Frame: 0, 60 and 90 minutes ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of blood lactate measured at the start and the finish of 1 hour of submaximal exercise at 50% VO2 MAX and then 30 minutes following this exercise

  • NEFA (Non-esterified fatty acids) [ Time Frame: 0, 60 and 90 minutes ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of NEFA in blood measured at the start and the finish of 1 hour of submaximal exercise at 50% VO2 MAX and then 30 minutes following this exercise

  • B-OHB (beta-hydroxybutyrate) [ Time Frame: 0, 60 and 90 minutes ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of beta-hydroxybutyrate in blood measured at the start and the finish of 1 hour of submaximal exercise at 50% VO2 MAX and then 30 minutes following this exercise

  • Catecholamines [ Time Frame: 0, 60 and 90 minutes ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of catecholamines in blood measured at the start and the finish of 1 hour of submaximal exercise at 50% VO2 MAX and then 30 minutes following this exercise

  • Glucagon [ Time Frame: 0, 60 and 90 minutes ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of glucagon in blood measured at the start and the finish of 1 hour of submaximal exercise at 50% VO2 MAX and then 30 minutes following this exercise

  • Human growth hormone (hGH) [ Time Frame: 0, 60 and 90 minutes ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of human Growth Hormone in blood measured at the start and the finish of 1 hour of submaximal exercise at 50% VO2 MAX and then 30 minutes following this exercise

  • Cortisol [ Time Frame: 0, 60 and 90 minutes ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of cortisol in blood measured at the start and the finish of 1 hour of submaximal exercise at 50% VO2 MAX and then 30 minutes following this exercise

  • IL-6 (interleukin 6) [ Time Frame: 0, 60 and 90 minutes ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of IL-6 in blood measured at the start and the finish of 1 hour of submaximal exercise at 50% VO2 MAX and then 30 minutes following this exercise

  • High sensitivity CRP (Hs-CRP) [ Time Frame: 0, 60 and 90 minutes ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of Hs-CRP in blood measured at the start and the finish of 1 hour of submaximal exercise at 50% VO2 MAX and then 30 minutes following this exercise

  • RQ (Respiratory Quotient) [ Time Frame: Baseline and 1 hour ] [ Designated as safety issue: No ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of the ratio of RQ measured at the start of exercise to the RQ at the end of 1 hour of submaximal exercise at 50% VO2 MAX

  • Frequency of hypoglycaemic events [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of the frequency of hypoglycaemic events (defined as blood glucose < 3.5mmol/l) between the start of 1 hour of exercise at 50% VO2 MAX and 24 hours after the end of this exercise.

  • Time spent in hypoglycaemia [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of the time spent in hypoglycaemia (blood glucose <3.5 mmol/l) between the start of 1 hour of exercise at 50% VO2 MAX and 24 hours after the end of this exercise

  • Blood glucose [ Time Frame: 0, 10, 20, 30, 40, 50, 60, 70, 80, 90 minutes ] [ Designated as safety issue: Yes ]
    This measure consists of a comparison between the two conditions (treatment with insulin glargine and treatment with insulin detemir) of blood glucose levels measured every 10 minutes from the start of 1 hour of submaximal exercise at 50% VO2 MAX until 30 minutes following this exercise


Estimated Enrollment: 30
Study Start Date: November 2011
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Insulin detemir
Metabolism during and after submaximal exercise during treatment with insulin detemir
Drug: Insulin detemir
Use of insulin detemir as basal insulin for treatment of Type 1 Diabetes Mellitus
Other Name: Levemir
Active Comparator: Insulin glargine
Metabolism during and after submaximal exercise during treatment with insulin glargine
Drug: Insulin glargine
Use of insulin glargine as basal insulin for treatment of Type 1 Diabetes Mellitus
Other Name: Lantus

Detailed Description:

A1: At the first appointment, potential participants will be screened regarding the inclusion criteria, and if eligible to take part the study information sheet will be discussed with them in detail. Written, informed consent will be obtained if participants are willing to take part in the study. Participants will be given advice and support from this point in order to optimise basal insulin therapy using their usual basal insulin.

A2: Following a period of at least 3 weeks from recruitment into the study, participants will have their maximal oxygen uptake (VO2 MAX - a measure of capacity for physical exercise) assessed.

A3: After at least 4 weeks following recruitment , to allow time for optimisation of basal insulin therapy, and at least one week following A2, the participant's metabolism will then be assessed during and after 60 minutes of exercise at 50% VO2 MAX. Participants will be fitted with a continuous glucose monitoring system (CGMS) to monitor glucose levels for the 24 hours after exercise finishes.

A4: At least 24 hours and no more than 7 days after A3 the participant will switched to using the other trial insulin for basal insulin therapy. Again, participants will be provided with advice and support in order to optimise treatment.

A5: At least 4 weeks following A4, the participant's metabolism will once again be assessed during and after 60 minutes of exercise at 50% VO2 MAX. Participants will again be fitted with CGMS to monitor glucose levels for the 24 hours after exercise finishes.

A6: Once the 24 hours after exercise are complete, the study finishes and participants re-start their usual basal insulin.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant is willing and able to give informed consent for participation in the study.
  • Male or Female, aged between 18 and 65 years
  • Diagnosed with Type 1 Diabetes Mellitus (T1DM)
  • HbA1c < 10% or 86 mmol/mol
  • Treated with a basal bolus regimen using either insulin glargine or insulin detemir as the basal insulin
  • Exercising regularly for at least 1 hour per week on average

Exclusion Criteria:

  • People with any one of the following complications of diabetes:

    • stage 2+ diabetic retinopathy
    • renal impairment (with creatinine >150micromol/l)
    • known history or symptoms of cardiovascular disease
    • foot ulceration
    • peripheral vascular disease
  • Pregnancy or breastfeeding
  • Untreated or unstable respiratory disease
  • Known hypoglycaemia unawareness
  • Treatment with drugs known to interfere with glucose metabolism
  • Known or suspected allergy to or intolerance of any of the trial drugs or related products
  • Receipt of any investigational drug within four months prior to Visit 0
  • Known or suspected abuse of alcohol, narcotics or illicit drugs
  • Any clinically significant disease or disorder which in the investigator's opinion could interfere with the results of the trial
  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: NCT01440439

Contacts
Contact: Alistair N Lumb, MBBS MRCP +441494425349/+44757007703 sportsdiabetes@hotmail.co.uk

Locations
United Kingdom
Wycombe Hospital Recruiting
High Wycombe, Buckinghamshire, United Kingdom, HP11 2TT
Sponsors and Collaborators
Buckinghamshire Healthcare NHS Trust
Novo Nordisk A/S
Investigators
Principal Investigator: Ian W Gallen, MD FRCP Bcukinghamshire Healthcare NHS Trust
  More Information

No publications provided

Responsible Party: Buckinghamshire Healthcare NHS Trust
ClinicalTrials.gov Identifier: NCT01440439     History of Changes
Other Study ID Numbers: RXQ425, 2011-001209-28, U1111-1119-8890
Study First Received: September 20, 2011
Last Updated: November 7, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Buckinghamshire Healthcare NHS Trust:
insulin glargine
insulin detemir
hypoglycaemia
metabolism
Exercise

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

ClinicalTrials.gov processed this record on September 18, 2014