EMPOWIR:Enhance the Metabolic Profile of Women With Insulin Resistance

NCT00618072 | Completed Phase 2 Results DMC

• 2 other identifiers: GSK-109157GSK CRN: 007674
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the study is to identify and treat women with midlife weight gain who have normal blood sugars, but increased insulin levels (hyperinsulinemia) following the performance of a glucose tolerance test. The study will evaluate effects of a unique carbohydrate modified diet alone and in combination with metformin(MF) and Avandamet® (MF plus rosiglitazone (RSG)) on insulin levels in a wide range of ethnically diverse women (aged 35-55) at three academic medical centers. The primary study hypothesis is that insulin sensitizing medications, in combination with alterations in carbohydrate intake, will reduce insulin levels and improve established risk factors for the metabolic syndrome. The alarming prevalence of obesity, diabetes, and related comorbidities and the paucity of easily adopted, cost-effective preventive strategies for high risk populations, suggest that pharmaco-therapies and dietary regimens targeted to reducing insulin resistance could have important clinical and public health implications.

Conditions

Hyperinsulinemia; Insulin Resistance; Obesity

Keywords

hyperinsulinemia; insulin resistance; perimenopause; obesity; overweight; women

Outcome Measures

Primary Outcomes (1)

• Fasting Insulin

  Insulin was determined with a Siemens Immulite assay with respective intra-and inter-CV's 5.7 and 5.9%, and no cross reactivity to pro-insulin.

  6 months

Secondary Outcomes (8)

• Body Weight

  6 months

• HOMA-IR

  6 months

• Waist Circumference

  6 months

• Systolic BP

  6 months

• Diastolic BP

  6 months

Study Arms (3)

A: Study diet

PLACEBO COMPARATOR

EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Drug: metformin and rosiglitazone

B: Study diet plus Metformin

ACTIVE COMPARATOR

Metformin and Rosiglitazone Placebo EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Drug: metformin and rosiglitazone

C: Study diet plus metformin and avandia

ACTIVE COMPARATOR

Metformin and Rosiglitazone EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Drug: metformin and rosiglitazone

Interventions

metformin and rosiglitazone DRUG

4 week dosage escalation of metformin, 500 mg/day (or placebo) to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day(or placebo) added at weeks 3 and weeks 4 to a a total dose of 4 mg/day

Also known as: glucophage, avandia, avandamet

A: Study diet; B: Study diet plus Metformin; C: Study diet plus metformin and avandia

Eligibility Criteria

• Age: 35 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, non-diabetic women with "≥20 pound weight gain since their twenties"
• Age: 35-55
• Peri-menopausal or postmenopausal status
• Body Mass Index (BMI) 25-35 kg/m2
• Either:
• a single blood pressure recording ≥135/85 or the use of blood pressure medication OR
• HDL≤50mg/dl or triglycerides ≥150 mg/dl or the use of lipid modifying medication
• Area-under-the-curve (AUC-)insulin level\>100mcgU/ml along with normal fasting (≤100 mg/dl) \& postprandial ((≤200 mg/dl) glucose determinations following a 75-gram standard oral glucose tolerance test.

You may not qualify if:

• known diabetes, fasting blood sugar ≥100 mg/dl or HbA-1-C≥6.0%
• known hepatic disease or ALT\>40
• known renal disease or creatinine ≥ 1.4
• known severe pulmonary disease
• chronic acidosis of any etiology
• Congestive heart failure (NYS Category 1), treated or untreated
• Cancer - active within 5 years
• current alcoholism or other substance abuse
• co-morbid psychiatric disorder, which in the opinion of the screening physician would require concomitant psychotherapy as part of obesity management
• currently untreated thyroid abnormality (TSH≤0.2 or ≥4mIU/L)
• pregnancy or contemplation of pregnancy
• use of TZD or metformin within the past year
• allergy to TZD or biguanide
• use of FDA approved or alternate obesity agent within 6 months of the study
• history of pseudotumor cerebri

Sponsors & Collaborators

• New York Medical College: lead
• Albert Einstein College of Medicine: collaborator
• University of Tennessee: collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Related Publications (6)

• Mogul HR, Peterson SJ, Weinstein BI, Zhang S, Southren AL. Metformin and carbohydrate-modified diet: a novel obesity treatment protocol: preliminary findings from a case series of nondiabetic women with midlife weight gain and hyperinsulinemia. Heart Dis. 2001 Sep-Oct;3(5):285-92. doi: 10.1097/00132580-200109000-00002.

  PMID: 11975807 BACKGROUND

• Mogul HR, Weinstein BI, Mogul DB, Peterson SJ, Zhang S, Frey M, Gambert SR, Southren AL. Syndrome W: a new model of hyperinsulinemia, hypertension and midlife weight gain in healthy women with normal glucose tolerance. Heart Dis. 2002 Mar-Apr;4(2):78-85. doi: 10.1097/00132580-200203000-00004.

  PMID: 11975838 BACKGROUND

• Mogul HR, Peterson SJ, Weinstein BI, Li J, Southren AL. Long-term (2-4 year) weight reduction with metformin plus carbohydrate-modified diet in euglycemic, hyperinsulinemic, midlife women (Syndrome W). Heart Dis. 2003 Nov-Dec;5(6):384-92. doi: 10.1097/01.hdx.0000098361.84908.9c.

  PMID: 14633321 BACKGROUND

• Mogul HR, Marshall M, Frey M, Burke HB, Wynn PS, Wilker S, Southern AL, Gambert SR. Insulin like growth factor-binding protein-1 as a marker for hyperinsulinemia in obese menopausal women. J Clin Endocrinol Metab. 1996 Dec;81(12):4492-5. doi: 10.1210/jcem.81.12.8954066.

  PMID: 8954066 BACKGROUND

• Mogul H, Freeman R, Nguyen K. METFORMIN-SUSTAINED WEIGHT LOSS AND REDUCED ANDROID FAT TISSUE AT 12 MONTHS IN EMPOWIR (ENHANCE THE METABOLIC PROFILE OF WOMEN WITH INSULIN RESISTANCE): A DOUBLE BLIND, PLACEBO-CONTROLLED, RANDOMIZED TRIAL OF NORMOGLYCEMIC WOMEN WITH MIDLIFE WEIGHT GAIN. Endocr Pract. 2016 May;22(5):575-86. doi: 10.4158/EP151087.OR. Epub 2016 Jan 20.

  PMID: 26789348 DERIVED

• Mogul HR, Freeman R, Nguyen K, Frey M, Klein LA, Jozak S, Tanenbaum K. Carbohydrate modified diet & insulin sensitizers reduce body weight & modulate metabolic syndrome measures in EMPOWIR (enhance the metabolic profile of women with insulin resistance): a randomized trial of normoglycemic women with midlife weight gain. PLoS One. 2014 Sep 26;9(9):e108264. doi: 10.1371/journal.pone.0108264. eCollection 2014.

  PMID: 25259787 DERIVED

MeSH Terms

Conditions

Hyperinsulinism; Insulin Resistance; Obesity; Overweight

Interventions

rosiglitazone-metformin combination; Metformin; Rosiglitazone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Widespread media coverage of cardiovascular risks of rosiglitazone led to an unanticipated high drop out rate of subjects just prior to their randomization; 22 of 68 eligible subjects did not undergo randomization due to concerns about the drug.

Results Point of Contact

• Title: Harriette R. Mogul MD MPH
• Organization: New York Medical College

Harriette_Mogul@NYMC.edu

914-594-2278

Study Officials

• Harriette R Mogul, MD MPH

  New York Medical College

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Research< Division of Adult Endocrinology

Study Record Dates

• First Submitted: February 5, 2008
• First Posted: February 18, 2008
• Study Start: January 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: March 28, 2014
• Results First Posted: March 28, 2014

Record last verified: 2014-03

Locations

US (1)