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HyperinsulinemiaPhase 2EMPOWIRNCT00618072

EMPOWIR:Enhance the Metabolic Profile of Women With Insulin Resistance

A Phase 2 study testing metformin and rosiglitazone in people with Hyperinsulinemia and Insulin Resistance, run by New York Medical College at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 35 to 55 years, women onlyHealthy volunteers can take part
Conditions the study is for
Hyperinsulinemia, Insulin Resistance, Obesity
What is being tested?
metformin and rosiglitazone
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
46 participants
Where
1 siteUnited States
Study dates
Jan 2008to Jan 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 to 55 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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.
  • -

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

Other trials in United States

About this study

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)

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.

Read the 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

Being tested
metformin and rosiglitazone
Keywords
hyperinsulinemia, insulin resistance, perimenopause, obesity, overweight, women
Medical subject headings
Hyperinsulinism, Insulin Resistance, Obesity, Overweight

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • metformin and rosiglitazoneDrug

    Also called glucophage, avandia, avandamet

    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

Study groups in NCT00618072
Study groupRoleWhat they receive
A: Study dietPlacebo comparatorEMPOWIR 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.
Receives: Drug: metformin and rosiglitazone
B: Study diet plus MetforminActive comparatorMetformin 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.
Receives: Drug: metformin and rosiglitazone
C: Study diet plus metformin and avandiaActive comparatorMetformin 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.
Receives: Drug: metformin and rosiglitazone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months

Secondary outcomes (8)
  1. Body Weight

    Body weight measurement was performed three times and averaged by a single study coordinator.

    Measured: 6 months

  2. HOMA-IR

    HOMA-IR was calculated by the formula: fasting insulin (uU/mL) times fasting glucose (mg/L) divided by 22.5.

    Measured: 6 months

  3. Waist Circumference

    Measured: 6 months

  4. Systolic BP

    Blood pressure was assessed using NCEP guidelines.

    Measured: 6 months

  5. Diastolic BP

    Blood pressure was assessed using NCEP guidelines.

    Measured: 6 months

  6. HDL

    HDL was measured using two reagents homogeneous systems with selective detergents to homogenize the lipoprotein of interest.

    Measured: 6 months

  7. Triglycerides

    Triglycerides were measured by enzymatic immunoassay on an AU400 chemistry auto-analyzer with commercially available enzymatic reagents.

    Measured: 6 months

  8. Adiponectin

    Total adiponectin was measured with a commercial ELISA kit (Millipore/Linco Research, St. Charles, MO) in the laboratory of Dr. Philipp Scherer.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2008 (estimated)
  2. Study startJan 2008
  3. Primary completionJan 2011
  4. Study completionJan 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00618072
Sponsor's protocol ID
GSK-109157
Other IDs
GSK CRN: 007674
Acronym
EMPOWIR
Status last verified
Mar 2014
First submitted
5 Feb 2008
Last updated
28 Mar 2014
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 11975807
  • 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.

    PubMed 11975838
  • 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.

    PubMed 14633321
  • 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.

    PubMed 8954066
  • 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.

    PubMed 26789348
  • 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.

    PubMed 25259787

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing metformin and rosiglitazone in people with Hyperinsulinemia and Insulin Resistance, run by New York Medical College at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fasting Insulin (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00618072, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2014.

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