search
Back to results

EMPOWIR:Enhance the Metabolic Profile of Women With Insulin Resistance (EMPOWIR)

Primary Purpose

Hyperinsulinemia, Insulin Resistance, Obesity

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
metformin and rosiglitazone
Sponsored by
New York Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyperinsulinemia focused on measuring hyperinsulinemia, insulin resistance, perimenopause, obesity, overweight, women

Eligibility Criteria

35 Years - 55 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  1. Healthy, non-diabetic women with "≥20 pound weight gain since their twenties"
  2. Age: 35-55
  3. Peri-menopausal or postmenopausal status
  4. Body Mass Index (BMI) 25-35 kg/m2
  5. Either:

    1. a single blood pressure recording ≥135/85 or the use of blood pressure medication OR
    2. HDL≤50mg/dl or triglycerides ≥150 mg/dl or the use of lipid modifying medication
  6. 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.

    -

Exclusion Criteria:

  1. known diabetes, fasting blood sugar ≥100 mg/dl or HbA-1-C≥6.0%
  2. known hepatic disease or ALT>40
  3. known renal disease or creatinine ≥ 1.4
  4. known severe pulmonary disease
  5. chronic acidosis of any etiology
  6. Congestive heart failure (NYS Category 1), treated or untreated
  7. Cancer - active within 5 years
  8. current alcoholism or other substance abuse
  9. co-morbid psychiatric disorder, which in the opinion of the screening physician would require concomitant psychotherapy as part of obesity management
  10. currently untreated thyroid abnormality (TSH≤0.2 or ≥4mIU/L)
  11. pregnancy or contemplation of pregnancy
  12. use of TZD or metformin within the past year
  13. allergy to TZD or biguanide
  14. use of FDA approved or alternate obesity agent within 6 months of the study
  15. history of pseudotumor cerebri
  16. other impairment, such as a history of medication noncompliance, which in the judgment of the screening clinician, would preclude active study participation.
  17. history of known or suspected heart disease

Sites / Locations

  • Albert Einstein College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

A: Study diet

B: Study diet plus Metformin

C: Study diet plus metformin and avandia

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Body Weight
Body weight measurement was performed three times and averaged by a single study coordinator.
HOMA-IR
HOMA-IR was calculated by the formula: fasting insulin (uU/mL) times fasting glucose (mg/L) divided by 22.5.
Waist Circumference
Systolic BP
Blood pressure was assessed using NCEP guidelines.
Diastolic BP
Blood pressure was assessed using NCEP guidelines.
HDL
HDL was measured using two reagents homogeneous systems with selective detergents to homogenize the lipoprotein of interest.
Triglycerides
Triglycerides were measured by enzymatic immunoassay on an AU400 chemistry auto-analyzer with commercially available enzymatic reagents.
Adiponectin
Total adiponectin was measured with a commercial ELISA kit (Millipore/Linco Research, St. Charles, MO) in the laboratory of Dr. Philipp Scherer.

Full Information

First Posted
February 5, 2008
Last Updated
March 27, 2014
Sponsor
New York Medical College
Collaborators
Albert Einstein College of Medicine, University of Tennessee
search

1. Study Identification

Unique Protocol Identification Number
NCT00618072
Brief Title
EMPOWIR:Enhance the Metabolic Profile of Women With Insulin Resistance
Acronym
EMPOWIR
Official Title
EMPOWIR: Enhance the Metabolic Profile of Women With Insulin Resistance: Carbohydrate Modified Diet Alone and in Combination With Metformin or Metformin Plus Avandia in Non-diabetic Women With Midlife Weight Gain and Documented Insulin Elevations (Syndrome W)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York Medical College
Collaborators
Albert Einstein College of Medicine, University of Tennessee

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
Progressive weight gain that starts in the fourth and fifth decades is commonly reported by women from all ethnic and socio-economic groups. Our previous data suggest that, in large and diverse subpopulations of healthy-appearing women this midlife weight gain may represent the earliest clinical manifestation of insulin resistance - demarcated by increased insulin response curves in the presence of completely normal glucose tolerance tests. We termed the disorder Syndrome W to highlight its defining triad of weight gain, waist gain and white-coat hypertension in women and its role as an alphabetic and chronologic antecedent to the better known Syndrome X. As in other disorders of insulin action in younger women, including Polycystic Ovarian Syndrome (PCOS), early adrenarche, and precocious puberty, Syndrome W is, presumably, a harbinger of The Metabolic Syndrome and Type 2 diabetes at an early and optimal period for intervention. Preliminary data from our first pilot study suggested that metformin, in combination with a hypocaloric, low-fat, carbohydrate modified dietary program produced significant and sustainable weight loss in women with Syndrome W, with notable reductions in fasting insulin levels. These findings supported hypotheses that insulin elevation might be an antecedent, as well as a consequence, of weight gain, accounting for a progressive and intractable weight spiral as women transition from their forties to their sixties. Additional two to four year follow-up in an intention-to-treat analysis of consecutive women who lost ≥10% of their body weight after one year of the treatment regimen further suggests that this composite intervention prevents weight regain and the onset of overt glucose impairment. The protocol evolved from evaluation and treatment of several hundred patients seen in The Endocrine Faculty Practice over a ten year period and has been highly successful in a broad ethnic range of normo-glycemic, hyperinsulinemic subjects. These include midlife women with weight gain and overweight men with upper body obesity - populations which have not been comparably treated in prior studies which focus predominantly on subjects with discernible glycemic abnormalities. The magnitude and duration of the treatment effect suggest that more rigorous study should be undertaken with a randomized clinical trial. PPAR agonists including thiazolidinediones (TZD's) are a newer category of insulin sensitizers with increasingly wide and well-studied positive attributes, including redistribution of fat depots, increased adiponectin secretion, and reduction of inflammatory and proinflammatory markers. The combination of metformin and rosiglitazone (Avandamet®) is FDA-approved for the treatment of hyperglycemia in patients with Type 2 diabetes. Previous clinical research and recent laboratory data suggest that the two categories of insulin sensitizers have independent and additive mechanisms of action that could target and, ultimately, modulate the underlying pathogenesis of insulin resistance. Comparison studies suggest that TZD's may have a greater insulin sensitizing action and provide greater reduction in hyperinsulinemia than metformin. However, due to increased adipocyte expression (and possible other mechanisms), weight gain is a common and undesirable side effect of TZD treatment. The addition of metformin to rosiglitazone, along with dietary strategies that reduce endogenous insulin production could prove an ideal therapeutic option to attenuate insulin resistance and preserve ß-cell function in high risk individuals. Early initiation of this dual regimen in normoglycemic subjects with documented hyperinsulinemia could have profound implications for Syndrome W women and for an additional 25% of the adult US population estimated to have other manifestations of The Metabolic Syndrome. The primary study question addressed is whether dual treatment regimens which modulate insulin action can reduce hyperinsulinemia and insulin resistance in high risk, but healthy-appearing normoglycemic, hyperinsulinemic subjects identified because of progressive, intractable, midlife weight gain

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperinsulinemia, Insulin Resistance, Obesity
Keywords
hyperinsulinemia, insulin resistance, perimenopause, obesity, overweight, women

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: Study diet
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
B: Study diet plus Metformin
Arm Type
Active Comparator
Arm Description
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.
Arm Title
C: Study diet plus metformin and avandia
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
metformin and rosiglitazone
Other Intervention Name(s)
glucophage, avandia, avandamet
Intervention Description
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
Primary Outcome Measure Information:
Title
Fasting Insulin
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Body Weight
Description
Body weight measurement was performed three times and averaged by a single study coordinator.
Time Frame
6 months
Title
HOMA-IR
Description
HOMA-IR was calculated by the formula: fasting insulin (uU/mL) times fasting glucose (mg/L) divided by 22.5.
Time Frame
6 months
Title
Waist Circumference
Time Frame
6 months
Title
Systolic BP
Description
Blood pressure was assessed using NCEP guidelines.
Time Frame
6 months
Title
Diastolic BP
Description
Blood pressure was assessed using NCEP guidelines.
Time Frame
6 months
Title
HDL
Description
HDL was measured using two reagents homogeneous systems with selective detergents to homogenize the lipoprotein of interest.
Time Frame
6 months
Title
Triglycerides
Description
Triglycerides were measured by enzymatic immunoassay on an AU400 chemistry auto-analyzer with commercially available enzymatic reagents.
Time Frame
6 months
Title
Adiponectin
Description
Total adiponectin was measured with a commercial ELISA kit (Millipore/Linco Research, St. Charles, MO) in the laboratory of Dr. Philipp Scherer.
Time Frame
6 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. - Exclusion Criteria: 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 other impairment, such as a history of medication noncompliance, which in the judgment of the screening clinician, would preclude active study participation. history of known or suspected heart disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harriette R Mogul, MD MPH
Organizational Affiliation
New York Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11975807
Citation
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.
Results Reference
background
PubMed Identifier
11975838
Citation
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.
Results Reference
background
PubMed Identifier
14633321
Citation
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.
Results Reference
background
PubMed Identifier
8954066
Citation
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.
Results Reference
background
PubMed Identifier
26789348
Citation
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.
Results Reference
derived
PubMed Identifier
25259787
Citation
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.
Results Reference
derived

Learn more about this trial

EMPOWIR:Enhance the Metabolic Profile of Women With Insulin Resistance

We'll reach out to this number within 24 hrs