Insulin Detemir in Obesity Management (IDIOM)
The purpose of this study is to evaluate the effects of the medication insulin detemir on weight, brain function and mood, and on blood vessel and other risk factors for heart disease. The study will compare how diet and insulin detemir affect areas of the brain that are involved in food intake and the sense of pleasure people get from eating.
Participants will be randomized into one of 2 groups. Group 1 will follow a low calorie diet only. Group 2 will follow a low calorie diet and take insulin detemir.
The study is 26 weeks in length and include outpatient visits, inpatient visits, phone and email contact, questionnaires, diary collection, blood draw and procedures involving MRI and PET scans. There are 4 inpatient visits at the Vanderbilt Clinical Research Center (CRC). The inpatient visits require a one night 2 day stay on the CRC at Weeks 2, 6, 16, 26. During the weekly and bi-weekly outpatient visits participants will meet with the study nurse and dietitian.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Making an "Obese"Brain(and Body)Lean: Insulin Detemir,Monoamines,and Reward|
- Low dose basal insulin detemir will potentiate weight loss in obese patients with type 2 diabetes mellitus undergoing a hypocaloric diet intervention by improving dopamine signaling [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]Determine if low dose basal insulin detemir potentiates loss of total body weight and adipose tissue in obese patients with type 2 diabetes mellitus undergoing a hypocaloric diet intervention
- Neuropsychiatric functions [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
Determine the effect of low dose basal insulin detemir (both dependent and independent of weight loss/composition) on relevant metabolic outcomes including:
insulin sensitivity and beta cell response as measured by oral glucose tolerance test, fasting lipids, markers of inflammation and coagulation, measurements of endothelial function, and neuroendocrine hormones.
Determine the effect of low dose basal insulin detemir on measures of that are effected by dopamine signaling including depression and mood, cognitive function, feeding related behavior, and personality including impulsivity.
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Insulin Detemir Treatment
Insulin detemir treatment: Insulin detemir will be administered subcutaneously, once daily. Dose ranges from approximately 0.1 U/kg up to 0.6 u/kg or higher. The dosing regimen will employ a strategy similar to the "303"algorithm, where, with close interaction with study personnel (rather than self-titration), bedtime insulin dosing will be titrated up by 3 units until AM fasting sugars within the prescribed protocol range are achieved (90-110 mg/dl). Subjects will have contact with study personnel on weekly basis for glycemia monitoring and adjustments. Similarly, documented hypoglycemia (blood sugars less than 70) will trigger a dose reduction, and it is expected that with weight loss, tolerable insulin dosages will drift downward. The treatment period is 24 weeks.
Subjects randomized to insulin detemir treatment group will receive the basal insulin in a 3 mL. Flex Pen® containing 300 units of insulin. insulin detemir once daily administered with the evening meal (dinner) or at bedtime as add-on to their oral antihyperglycemia (see inclusion/exclusion criteria) meds throughout the 24 week treatment period. The goal of insulin therapy is to achieve near normoglycemia with a low rate of hypoglycaemic episodes.
Insulin injections will be given subcutaneously preferably in the thigh or abdomen.
Other Name: Levemir
No Intervention: Comparator: No insulin
The main hypothesis is that "diabetes can be changed " with early and careful insulinization capturing effects on brain function ultimately leading to weight loss. . Seek to determine in a quantitative manner whether insulin detemir restores brain dopamine neurotransmission, a control group not treated with insulin is required. The strength of this study is our ability to test the specific molecular (D2R, DAT, functional MRI responses) and integrated output (functional brain responses, mood, cognitive function, reward responses etc.) of CNS dopaminergic pathways in order to shed unprecedented light upon mechanisms of detemir action in obesity and diabetes.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01239550
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Kevin D Niswender, MD/PhD||Vanderbilt University|