Insulin Detemir in Obesity Management

NCT01239550 | Active Not Recruiting DMC

• 1 other identifier: KDN2010
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes; Obesity

Keywords

Insulin; Detemir; Dopamine, brain,neurotransmitter; Diabetes; Obesity; Neurotransmitters

Outcome Measures

Primary Outcomes (1)

• 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

  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

  26 weeks

Secondary Outcomes (1)

• Neuropsychiatric functions

  26 weeks

Study Arms (2)

Insulin Detemir Treatment

EXPERIMENTAL

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

Comparator: No insulin

NO INTERVENTION

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.

Interventions

Detemir DRUG

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.

Also known as: Levemir

Insulin Detemir Treatment

Eligibility Criteria

• Age: 31 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Informed consent obtained before any trial-related activities
• Age at study entry is between 31-60 years of age
• Body Mass index (BMI) between 30-49 kg/m2 using measured height and weight
• Body weight \<350lbs (MRI table limit)
• Stable body weight during the previous 3 months with a less than 5 pounds self -reported weight change
• 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)
• HbA1c level between \~6-8%
• Lives in a community dwelling and has a telephone
• 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.
• Able and willing to follow prescribed menus plans

You may not qualify if:

• Known or suspected hypersensitivity to study drug (insulin detemir)
• Significant co-morbidities including cardiovascular disease, atherosclerotic disease, pulmonary disease, metabolic disease, liver or renal insufficiency
• 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).
• Clinically significant abnormalities on screening EKG
• History of Substance Abuse, including but not exclusive to alcohol, cocaine, marijuana, heroin, nicotine
• Any tobacco use in last 3 months
• 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
• 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).
• Inability to abstain from alcohol, physical exercise or \> 1 cup of coffee or equivalent daily for 2 days prior to imaging studies
• 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)
• History of uncontrolled thyroid disease evidenced by TSH outside normal range
• Obesity induced by other endocrinologic disorders (e.g. Cushing Syndrome, Polycystic ovarian syndrome)
• Previous surgery for weight loss
• High level aerobic activity such as running for longer than 60 minutes more than 2 times a week regularly in last 3months
• Significant eating disorder or dietary restraints as determined by three factor eating questionnaire (TFEQ)

Sponsors & Collaborators

• Vanderbilt University: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Lillegard K, Del Castillo JA, Silver HJ. Poorly controlled glycemia and worse beta cell function associate with higher resting and total energy expenditure in adults with obesity and type 2 diabetes: A doubly labeled water study. Clin Nutr. 2024 Mar;43(3):729-738. doi: 10.1016/j.clnu.2024.01.011. Epub 2024 Jan 17.

  PMID: 38320464 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Obesity; Insulin Resistance

Interventions

Insulin Detemir

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Kevin D Niswender, MD/PhD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 9, 2010
• First Posted: November 11, 2010
• Study Start: April 1, 2011
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (1)