Insulin Detemir in Obesity Management (IDIOM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Vanderbilt University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Wanda Snead, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01239550
First received: November 9, 2010
Last updated: June 21, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention
Diabetes
Obesity
Drug: Detemir

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.



Estimated Enrollment: 240
Study Start Date: April 2011
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Detemir

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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  Eligibility

Ages Eligible for Study:   31 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Informed consent obtained before any trial-related activities
  2. Age at study entry is between 31-60 years of age
  3. Body Mass index (BMI) between 30-49 kg/m2 using measured height and weight
  4. Body weight <350lbs (MRI table limit)
  5. Stable body weight during the previous 3 months with a less than 5 pounds self -reported weight change
  6. Type 2 diabetes, insulin naïve (except for use during gestational diabetes) on either metformin, sitagliptin, or dipeptidyl-4 inhibitor (sitagliptin or saxagliptin), or a thiazolidines (rosiglitazone or pioglitazone)
  7. HbA1c level between ~6-8%
  8. Lives in a community dwelling and has a telephone
  9. Agrees to avoid alcohol and exercise within 48 hours of CRC visits, and to comply with the dietary/stimulant restrictions for 48 hours before PET and fMRI studies.
  10. Able and willing to follow prescribed menus plans

Exclusion Criteria:

  1. Known or suspected hypersensitivity to study drug (insulin detemir)
  2. Significant co-morbidities including cardiovascular disease, atherosclerotic disease, pulmonary disease, metabolic disease, liver or renal insufficiency
  3. Significant pathologic finding on MRI (research MRI scans are not clinical scans and are not standardly read by a neuroradiologist, but if an overt anomaly is noted by study personnel, an advisory read will be obtained and the patient will be provided with the information for follow-up with his/her physician).
  4. Clinically significant abnormalities on screening EKG
  5. History of Substance Abuse, including but not exclusive to alcohol, cocaine, marijuana, heroin, nicotine
  6. Any tobacco use in last 3 months
  7. History of psychiatric disorder deemed too severe to permit participation (PI discretion) including subjects with a lifetime history of lifetime Psychotic Disorder (Schizophrenia, Schizoaffective, Psychosis NOS) or Bipolar Disorder, suicide attempt or history of any suicidal behavior or history within the past 6 months of Post Traumatic Stress Disorder, Generalized Anxiety Disorder
  8. Long term use of steroids or medications that may cause weight gain within 3 months of study or in foreseeable need (e.g. uncontrolled asthma or rheumatologic disorder).
  9. Inability to abstain from alcohol, physical exercise or > 1 cup of coffee or equivalent daily for 2 days prior to imaging studies
  10. Any contraindication which would interfere with MRI or PET studies, e.g. claustrophobia, cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body
  11. Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (abstinence or the following methods: diaphragm with spermicide, condom with spermicide by male partner, intrauterine device, sponge, spermicide, Norplant, Depo-Provera or oral contraceptives)
  12. History of uncontrolled thyroid disease evidenced by TSH outside normal range
  13. Obesity induced by other endocrinologic disorders (e.g. Cushing Syndrome, Polycystic ovarian syndrome)
  14. Previous surgery for weight loss
  15. High level aerobic activity such as running for longer than 60 minutes more than 2 times a week regularly in last 3months
  16. Significant eating disorder or dietary restraints as determined by three factor eating questionnaire (TFEQ)
  17. Appetite reducing diet supplement or herbal supplement use in last 6 months
  18. . Food allergy or diet restrictions that would interfere with balanced intake and caloric goals.
  19. Dietary supplements of such as EPA, DHA or omega-3 fatty acids.
  20. Daily intakes of coffee, black tea and other caffeinated beverages will be assessed and subjects who consume the equivalent of >4 cups coffee or black tea/day at baseline will be excluded
  21. Any condition felt by PI or co-investigators to interfere with ability to complete the study
  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: NCT01239550

Contacts
Contact: Wanda Snead, Dr. HSc 615-936-1625 wanda.snead@vanderbilt.edu
Contact: Antoinette L. Richardson, RN 615-936-1146 antoinette.richardson@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Wanda L. Snead, Dr. HSc    615-936-1625    wanda.snead@vanderbilt.edu   
Contact: Antoinette Richardson, RN    615-936-5144    m.a.richardson@vanderbilt.edu   
Principal Investigator: Kevin D Niswender, MD/PhD         
Sponsors and Collaborators
Vanderbilt University
Novo Nordisk A/S
Investigators
Principal Investigator: Kevin D Niswender, MD/PhD Vanderbilt University
  More Information

No publications provided

Responsible Party: Wanda Snead, Research Instructor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01239550     History of Changes
Other Study ID Numbers: KDN2010
Study First Received: November 9, 2010
Last Updated: June 21, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Insulin
Detemir
Dopamine, brain,neurotransmitter
Diabetes
Obesity
Neurotransmitters

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Insulin, Globin Zinc
Insulin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014