Effect of a Basal/Pre-Meal Insulin Strategy (Detemir/Aspart) on Insulin Secretion and Action in Type 2 Diabetes

NCT00998335 | Completed Phase 4 Results

• 1 other identifier: 20060167
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The optimal insulin therapy in T2DM is controversial and its impact on nonalcoholic fatty liver disease (NAFLD) has not been systematically studied before, and in particular, never when using the new insulin formulations detemir (Levemir®) or aspart (Novolog®). This study is to determine the effect on hepatic steatosis and insulin secretion/action of lowering the fasting plasma glucose (FPG) to target with once daily basal insulin detemir alone or combining insulin detemir with premeal insulin aspart in patients with uncontrolled type 2 diabetes mellitus (T2DM). In the first 3 months the investigators will optimize metabolic control in all patients with intensive basal (bedtime) detemir insulin aiming at a normal fasting plasma glucose. After this treatment period, patients will be randomized in the second 3 months in a 2:1 ratio to insulin detemir or detemir plus aspart. The investigators propose that insulin will improve day-long glycemic control and A1c, reduce hepatic steatosis (NAFLD) (primary endpoint) and insulin secretion/sensitivity being well tolerated while causing minimal weight gain and hypoglycemia (secondary endpoints). The study will allow to assess if there is an additional benefit of adding pre-meal rapid-acting insulin aspart to basal insulin to these endpoints.

Conditions

Type 2 Diabetes

Keywords

Type 2 diabetes mellitus; Insulin therapy; Detemir (Levemir); Aspart (Novolog); Hepatic steatosis

Outcome Measures

Primary Outcomes (1)

• Hepatic Steatosis

  Hepatic steatosis measured by proton magnetic resonance spectroscopy (1H-MRS).

  3 and 6 months

Secondary Outcomes (11)

• Metabolic Control as Measured by the A1c

  3 and 6 months

• Change in Insulin Secretion

  3 and 6 months.

• Intramyocellular (IMCL) by Magnetic Resonance Imaging and Spectroscopy (MRS).

  3 and 6 months.

• Plasma Lipid Concentration.

  3 and 6 months.

• Change in Anthropometric Measure (Body Weight).

  3 and 6 months.

Study Arms (2)

Insulin detemir only

ACTIVE COMPARATOR

Patients with uncontrolled T2DM are treated with insulin detemir for 6 months. Insulin detemir is given at bedtime aiming at a fasting plasma glucose between 80-100 mg/dl. This group will receive Long-acting bedtime insulin detemir (Levemir).

Drug: Long-acting bedtime insulin detemir (Levemir)

Insulin detemir plus aspart

EXPERIMENTAL

After baseline evaluations, insulin detemir will be given at bedtime and titrated to achieve a fasting plasma glucose between 80-100 mg/dl. After 3 months patients will be admitted to assess the metabolic effects of intervention. After this, insulin aspart (insulin detemir plus aspart) will be added before breakfast, lunch and dinner titrated to normalize the postprandial plasma glucose. After another 3 months patients are readmitted and all study procedures repeated. This group will receive Insulin detemir and pre-meal insulin aspart.

Drug: Insulin detemir and pre-meal insulin aspart.

Interventions

Long-acting bedtime insulin detemir (Levemir) DRUG

This group will receive Insulin detemir. Insulin detemir is given at bedtime aiming at a fasting plasma glucose between 80-100 mg/dl.

Also known as: Levemir insulin (trademark insulin by Novo Nordisk)

Insulin detemir only

Insulin detemir and pre-meal insulin aspart. DRUG

This group will receive Insulin detemir plus aspart. The group will start with Insulin detemir at bedtime. Then in three months they will Insulin aspart before breakfast, lunch and dinner.

Also known as: Insulin detemir = Levemir (Novo Nordisk), Insulin aspart = Novolog (Novo Nordisk)

Insulin detemir plus aspart

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To participate patients must:
• Be able to communicate meaningfully with the Investigator and be legally competent to provide written informed consent.
• Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy are eligible for participation in the study. Female patients (except for those patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period.
• Age range of 18 to 70 years (inclusive).
• Patients must have been on a stable dose of allowed chronic medications for two months prior to entering the double-blind treatment period.
• All participants must have the following laboratory values:
• Hemoglobin ≥ 12 g/dl in males or ≥ 11 g/dl in females
• Serum creatinine ≤ 1.5 mg/dl
• AST (SGOT) ≤ 2.5 times upper limit of normal
• ALT (SGPT) ≤ 2.5 times upper limit of normal
• Alkaline phosphatase ≤ 2.5 times upper limit of normal

You may not qualify if:

• Patients will be excluded if any of the following criteria are present:
• Individuals with type 1 diabetes or type 2 diabetes and a FPG ≥ 300 mg/dl.
• Subjects on sulfonylureas, metformin and/or TZDs unless the dose has been stable for at least 2 months prior to study entry.
• Patients on any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on stable doses of such agents for the past two months before entry into the study. Patients may be taking stable doses of estrogens or other hormonal replacement therapy if the patient has been on these agents for the prior two months. Patients taking systemic glucocorticoids will be excluded.
• Past (within 1 year) or current history of alcohol abuse.
• Patients will be excluded if there is a history of clinically significant heart disease (New York Heart Classification greater than grade II), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) or chronic renal failure (serum creatinine greater than 1.5 mg/dl).

Sponsors & Collaborators

• University of Florida: lead
• VA Office of Research and Development: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (1)

The University of Texas H.S.C. at San Antonio and the San Antonio Audie L. Murphy VA Hospital

San Antonio, Texas, 78229-3900, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Fatty Liver

Interventions

Insulin Detemir

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Kenneth Cusi
• Organization: University of Florida

KCusi@ufl.edu

352-273-7236

Study Officials

• Kenneth Cusi, M.D.

  University of Flordia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2009
• First Posted: October 20, 2009
• Study Start: June 1, 2007
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: September 28, 2016
• Results First Posted: July 29, 2016

Record last verified: 2016-06

Locations

US (1)