Clinical trial NCT02417012: Lifestyle and Glucose Lowering Medication in T2DM
Official title: Does Intensive Life Style Intervention Reduce the Need for Glucose Lowering Medications in Patients With Type 2 Diabetes? The U-TURN Project
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Keywords: lifestyle
exercise
physical activity
diet
glycemic control
hba1c
glucose lowering drugs
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: TRYG Foundation
First posted: 2015-04-15
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the effect of a lifestyle intervention maintenance of glycemic control while reducing glucose lowering drugs in patients with type 2 diabetes mellitus. The intervention group receives an intensive lifestyle intervention including exercise and diet lifestyle modifications. The reference group receives diabetes educational advice. Both groups will have their pharmacological treatment regulated across the study. The primary hypothesis is that lifestyle change is sufficient to maintain glycemic control while decreasing the anti-diabetic medication in a sample patients with type 2 diabetes mellitus.

Detailed description: Adherence to lifestyle modifications including increased exercise and healthy diet improves glycemic control in patients with type 2 diabetes mellitus. However, few have investigated the combined effects of these lifestyle changes on maintenance of glycemic control while decreasing the usage of anti-diabetic medications.

The primary hypothesis is that lifestyle change is equivalent in maintaining glycemic control (Hba1c) compared to the standard pharmacological treatment,

The U-TURN trial also tests the effects on one key secondary outcome (glucose lowering medication) and examines the effects on sleep quality, fatigue sleepiness, sleep pattern, cardio vascular disease risk factors, psychological outcomes, blood pressure and cholesterol lowering medication. The participants (N=120) is randomized into a experimental group (N=80) and a standard care group (N=40).

Additionally, the effects of the study will be evaluated 24 month post randomization.

Eligibility criteria: Inclusion Criteria:

* Less than three anti-diabetic medications.
* Diabetes 2 duration of max 10 years
* BMI \>25 but \<40 kg/m2,
* Accept of medical regulation by the UTURN endocrinologists only
* Accept of purchasing a fitness club membership through U-TURN collaborator

Exclusion Criteria:

* Hba1c\> 9% (75 mmol/mol)
* Insulin usage
* Presence of one or more of the following micro- and macrovascular complications of T2DM; a.Diabetic retinopathy (except mild nonproliferative retinopathy or early proliferative retinopathy) b. Macro-albuminuria or nephropathy c. Diabetic neuropathy (except mild affected vibratory testing (\<50 Volt)) d. Arterial insufficiency e. Ischemic heart disease
* Steroid treatment (inhalation) until three months before the medical examination
* TSH raised/below the normal range
* Liver disease (ALAT/ASAT thrice normal range)
* Inability or contraindication to increased levels of physical activity (Pedersen BK and Saltin B)
* Evidence of anaemia
* Lung disease (except mild asthma and mild chronic obstructive pulmonary disease)
* Heart disease
* Kidney disease (creatinine above 130 µM or macro albuminuria)
* Pregnancy

Primary outcomes:
measure: Change in Hba1c
timeFrame: 0, 3, 6, 9, 12 months
Secondary outcomes:
measure: Change in glucose lowering medication
timeFrame: 0, 3, 6, 9, 12 months
Other outcomes:
measure: incidence of hypo-glycemic episodes
timeFrame: 0, 3, 6, 9, 12, 24 months
measure: Changes Ldl cholesterol
timeFrame: 0, 3, 6, 9, 12, 24 months
measure: Changes Hdl cholesterol
timeFrame: 0, 3, 6, 9, 12, 24 months
measure: Changes total cholesterol
timeFrame: 0, 3, 6, 9, 12, 24 months
measure: Changes in triglycerides
timeFrame: 0, 3, 6, 9, 12, 24 months
measure: Changes in bdnf-a
timeFrame: 0, 12 months
measure: Change in physical fitness
timeFrame: 0, 12, 24 months
measure: Change in body composition (DXA scan)
timeFrame: 0, 3, 6, 9, 12, 24 months
measure: Change in sleep quality
timeFrame: 0, 12, months
measure: Change in sleepiness
timeFrame: 0, 12, months
measure: Change in sleep pattern
timeFrame: 0, 12, months
measure: Change in the degree of depression
timeFrame: 0, 12, 24 months
measure: Change in Glucose tolerance (2-h oral glucose tolerance test)
timeFrame: 0, 12, 24 months
measure: Change in Well-being
timeFrame: 0, 12, 24 months
measure: Change in motivation for exercise
timeFrame: 0, 12, 24 months
measure: Change in cognitive function
timeFrame: 0, 12 months
measure: Change in arterial function
timeFrame: 0, 12 months
measure: Partial T2D remission
timeFrame: 24 months
measure: Full T2D remission
timeFrame: 24 months
measure: Change in low grade inflammation
timeFrame: 0, 12, 24 months
Locations:
city: Copenhagen
country: Denmark
facility: Center for Physical Activity Research, Copenhagen University Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Mathias Ried-Larsen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pedersen BK, Saltin B. Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports. 2006 Feb;16 Suppl 1:3-63. doi: 10.1111/j.1600-0838.2006.00520.x.
citation: Legaard GE, Feineis CS, Johansen MY, Hansen KB, Vaag AA, Larsen EL, Poulsen HE, Almdal TP, Karstoft K, Pedersen BK, Ried-Larsen M. Effects of an exercise-based lifestyle intervention on systemic markers of oxidative stress and advanced glycation endproducts in persons with type 2 diabetes: Secondary analysis of a randomised clinical trial. Free Radic Biol Med. 2022 Aug 1;188:328-336. doi: 10.1016/j.freeradbiomed.2022.06.013. Epub 2022 Jun 25.
citation: Abildgaard J, Johansen MY, Skov-Jeppesen K, Andersen LB, Karstoft K, Hansen KB, Hartmann B, Holst JJ, Pedersen BK, Ried-Larsen M. Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial. Med Sci Sports Exerc. 2022 Jan 1;54(1):38-46. doi: 10.1249/MSS.0000000000002776.
citation: MacDonald CS, Nielsen SM, Bjorner J, Johansen MY, Christensen R, Vaag A, Lieberman DE, Pedersen BK, Langberg H, Ried-Larsen M, Midtgaard J. One-year intensive lifestyle intervention and improvements in health-related quality of life and mental health in persons with type 2 diabetes: a secondary analysis of the U-TURN randomized controlled trial. BMJ Open Diabetes Res Care. 2021 Jan;9(1):e001840. doi: 10.1136/bmjdrc-2020-001840.
citation: Johansen MY, Karstoft K, MacDonald CS, Hansen KB, Ellingsgaard H, Hartmann B, Wewer Albrechtsen NJ, Vaag AA, Holst JJ, Pedersen BK, Ried-Larsen M. Effects of an intensive lifestyle intervention on the underlying mechanisms of improved glycaemic control in individuals with type 2 diabetes: a secondary analysis of a randomised clinical trial. Diabetologia. 2020 Nov;63(11):2410-2422. doi: 10.1007/s00125-020-05249-7. Epub 2020 Aug 20.
citation: MacDonald CS, Johansen MY, Nielsen SM, Christensen R, Hansen KB, Langberg H, Vaag AA, Karstoft K, Lieberman DE, Pedersen BK, Ried-Larsen M. Dose-Response Effects of Exercise on Glucose-Lowering Medications for Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial. Mayo Clin Proc. 2020 Mar;95(3):488-503. doi: 10.1016/j.mayocp.2019.09.005. Epub 2020 Jan 30.
citation: Johansen MY, MacDonald CS, Hansen KB, Karstoft K, Christensen R, Pedersen M, Hansen LS, Zacho M, Wedell-Neergaard AS, Nielsen ST, Iepsen UW, Langberg H, Vaag AA, Pedersen BK, Ried-Larsen M. Effect of an Intensive Lifestyle Intervention on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2017 Aug 15;318(7):637-646. doi: 10.1001/jama.2017.10169.
citation: Ried-Larsen M, Christensen R, Hansen KB, Johansen MY, Pedersen M, Zacho M, Hansen LS, Kofoed K, Thomsen K, Jensen MS, Nielsen RO, MacDonald C, Langberg H, Vaag AA, Pedersen BK, Karstoft K. Head-to-head comparison of intensive lifestyle intervention (U-TURN) versus conventional multifactorial care in patients with type 2 diabetes: protocol and rationale for an assessor-blinded, parallel group and randomised trial. BMJ Open. 2015 Dec 9;5(12):e009764. doi: 10.1136/bmjopen-2015-009764.