Insulin ResistancePhase 2NCT00123110
Insulin Resistance and Testosterone in Women
A Phase 2 study testing metformin and leuprolide injection in people with Insulin Resistance and Postmenopause, run by University of Pennsylvania at 1 site in United States.
Trial summary
The purpose of this research study is to determine if a relationship between insulin resistance (IR) and testosterone (T) exists in women who have already gone through menopause. Read more about this study
- Who is it for?
- Ages 50 to 79 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Postmenopause
- What is being tested?
- metformin and leuprolide injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2005to Dec 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 50 to 79 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Postmenopausal women aged 50-79 years with absence of menses for 12 months; for women 50-54 years, Follicle stimulating hormone>30 U/mL to confirm postmenopausal status
- At least one intact ovary
- Free testosterone and fasting insulin levels within required study parameters
- Willing to comply with all study-related procedures
- Capable of giving informed consent
Who cannot join
- History of cancer requiring treatment within the past 5 years (exceptions may be made by investigator)
- Hospitalization for treatment of vascular disease in the past 6 months
- Uncontrolled hypertension
- Hospitalization for chronic obstructive pulmonary disease or asthma in the past 3 months
- Use of continuous oxygen at home
- Surgery in the last 30 days
Show all 23Show fewer
- Positive for HIV
- Abnormal blood tests (hemoglobin, fasting triglycerides, fasting glucose, creatinine, liver function)
- History of diabetes mellitus or use of any anti-hyperglycemic medication in the past 3 months
- Disease associated with disordered glucose metabolism (Cushing's disease, acromegaly, pheochromocytoma not surgically cured, chronic pancreatitis)
- History of chronic renal insufficiency
- Intravenous (IV) contrast studies with iodinated materials planned for the 12 week intervention period that cannot be postponed according to the participant's primary care provider
- Acute or chronic metabolic acidosis
- History of liver disease
- Congestive heart failure
- History of androgen-secreting tumors
- Hormone replacement therapy or antiandrogen use in past 6 months
- Use of dehydroepiandosterone (DHEA) or other androgen-containing products in past 6 months
- Corticosteroid use, other than topical, ophthalmic, intraarticular, and inhaled preparations, in past 3 months
- Undiagnosed current vaginal bleeding
- Excessive alcohol intake, either acute or chronic; current illicit substance abuse
- Participation in an investigational drug study within 6 weeks prior to screening visit
- Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the patient's safety or successful participation in the study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania Clinical and Translational Research Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: Insulin Resistance and Testosterone in Non-Diabetic Postmenopausal Women
The purpose of this research study is to determine if a relationship between insulin resistance (IR) and testosterone (T) exists in women who have already gone through menopause.
Read the detailed description
This study tests the central hypothesis that insulin resistance (IR) increases androgen (male sex hormone) production in postmenopausal women. Participation will include five visits, each lasting on average 2.5 hours, over a period of 13-20 weeks.
At the screening visit, the participant's medical history, current use of medications and dietary supplements, and social habits will be recorded. This information will be reviewed on each subsequent visit; participants are asked to maintain their current diet and physical activity level throughout the study.
A brief physical exam will be performed, and blood will be drawn.
At the 2nd (baseline) visit, patients will undergo a euglycemic-hyperinsulinemic clamp (a procedure to measure insulin sensitivity by continuous intravenous infusion of insulin, and variable infusion of glucose). Blood samples will be drawn throughout the procedure. At completion, the insulin infusion will be stopped, participants will be fed, and the glucose infusion continued for at least 15 minutes to ensure stability of the blood glucose concentration. After the procedure, participants will be randomized to receive either metformin plus leuprolide placebo, leuprolide plus metformin placebo, or metformin placebo plus leuprolide placebo. The leuprolide or leuprolide placebo will be administered as an injection by a nurse. The metformin or metformin placebo will be dispensed to the participant in the form of pills, with instructions for titrating the dose. Participants will be contacted by telephone once weekly during the titration period to assess drug tolerability and adverse events (AEs). Participants will be maintained at their maximum tolerated dose for the duration of the study intervention period.
Participants will return every 4 weeks for follow-up. Blood will be drawn, the nurse will administer the leuprolide or leuprolide placebo injection, and metformin or metformin placebo will be dispensed. At the final visit (week 12), participants will undergo a brief physical exam, and will then undergo a final euglycemic-hyperinsulinemic clamp.
- Conditions
- Insulin Resistance, Postmenopause
- Being tested
- metformin, leuprolide injection, placebo pill, placebo injection
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metforminDrug
Also called Glucophage
Initiated on 500 mg daily and titrated up to 1000 mg twice a day during the first four weeks, remaining at that dose until 12 weeks
leuprolide injectionDrug
Also called Lupron
3.75 mg injection every 4 weeks (e.g. at baseline, 4, and 8 weeks)
placebo pillDrug
matching pill twice a day for 12 weeks
placebo injectionDrug
matching injection every 4 weeks (e.g. baseline, 4, and 8 weeks)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | metformin pill plus placebo injection Receives: Drug: metformin; Drug: placebo injection |
| 2 | Experimental | leuprolide injection plus placebo pill Receives: Drug: leuprolide injection; Drug: placebo pill |
| 3 | Placebo comparator | placebo pill plus placebo injection Receives: Drug: placebo pill; Drug: placebo injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Free Testosterone (T)
Percent change in free T by equilibrium dialysis between baseline and 12 weeks
Measured: Baseline to 12 weeks
Change in Insulin Sensitivity
Change in insulin sensitivity (mg/kg/min) calculated from hyperinsulinemic euglycemic clamp
Measured: baseline and 12 weeks
Secondary outcomes (7)
Percent Change in Luteinizing Hormone (LH) From Baseline
Measured: baseline and 12 weeks
Percent Change in Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR)
Insulin resistance calculated from homeostasis model assessment of insulin resistance (HOMA-IR) equation: fasting insulin x fasting glucose / 405. Higher values indicate more insulin resistance.
Measured: baseline and 12 weeks
Percent Change in Low Density Lipoprotein (LDL)
Measured: baseline and 12 weeks
Percent Change in Systolic Blood Pressure
Measured: baseline and 12 weeks
Free T and IR in Women in Whom Metabolic Syndrome is Present vs. Absent
Measured: baseline and 12 weeks
Dehydroepiandrosterone Sulfate (DHEA-S)
Measured: baseline and 12 weeks
Body Mass Index (BMI)
Measured: baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2005 (estimated)
- Study startJul 2005
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA), The John A. Hartford Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Pennsylvania Diabetes and Endocrinology Research Center (DERC), TAP Pharmaceutical Products Inc.
- Responsible party
- Sponsor
- Investigators
- Anne R. Cappola, MD, ScM, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00123110
- Sponsor's protocol ID
- AG0031
- Other IDs
- K23AG019161, K23AG1916101A1, 5P30DK019525
- Status last verified
- May 2019
- First submitted
- 19 Jul 2005
- Last updated
- 23 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16;287(3):356-9. doi: 10.1001/jama.287.3.356.
PubMed 11790215Golden SH, Ding J, Szklo M, Schmidt MI, Duncan BB, Dobs A. Glucose and insulin components of the metabolic syndrome are associated with hyperandrogenism in postmenopausal women: the atherosclerosis risk in communities study. Am J Epidemiol. 2004 Sep 15;160(6):540-8. doi: 10.1093/aje/kwh250.
PubMed 15353414Larsson H, Ahren B. Androgen activity as a risk factor for impaired glucose tolerance in postmenopausal women. Diabetes Care. 1996 Dec;19(12):1399-403. doi: 10.2337/diacare.19.12.1399.
PubMed 8941471Oh JY, Barrett-Connor E, Wedick NM, Wingard DL; Rancho Bernardo Study. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care. 2002 Jan;25(1):55-60. doi: 10.2337/diacare.25.1.55.
PubMed 11772901
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Insulin Resistance and Testosterone in Non-Diabetic Postmenopausal Women
- ClinicalTrials.gov ID
- NCT00123110
- Acronym / sponsor ID
- AG0031
- Conditions
- Insulin Resistance, Postmenopause
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA), The John A. Hartford Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Pennsylvania Diabetes and Endocrinology Research Center (DERC), TAP Pharmaceutical Products Inc.
- Study start
- Jul 2005
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 22 Jul 2005 (estimated)
- Results
- Posted 23 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to determine if a relationship between insulin resistance (IR) and testosterone (T) exists in women who have already gone through menopause.
Detailed description
This study tests the central hypothesis that insulin resistance (IR) increases androgen (male sex hormone) production in postmenopausal women. Participation will include five visits, each lasting on average 2.5 hours, over a period of 13-20 weeks.
At the screening visit, the participant's medical history, current use of medications and dietary supplements, and social habits will be recorded. This information will be reviewed on each subsequent visit; participants are asked to maintain their current diet and physical activity level throughout the study.
A brief physical exam will be performed, and blood will be drawn.
At the 2nd (baseline) visit, patients will undergo a euglycemic-hyperinsulinemic clamp (a procedure to measure insulin sensitivity by continuous intravenous infusion of insulin, and variable infusion of glucose). Blood samples will be drawn throughout the procedure. At completion, the insulin infusion will be stopped, participants will be fed, and the glucose infusion continued for at least 15 minutes to ensure stability of the blood glucose concentration. After the procedure, participants will be randomized to receive either metformin plus leuprolide placebo, leuprolide plus metformin placebo, or metformin placebo plus leuprolide placebo. The leuprolide or leuprolide placebo will be administered as an injection by a nurse. The metformin or metformin placebo will be dispensed to the participant in the form of pills, with instructions for titrating the dose. Participants will be contacted by telephone once weekly during the titration period to assess drug tolerability and adverse events (AEs). Participants will be maintained at their maximum tolerated dose for the duration of the study intervention period.
Participants will return every 4 weeks for follow-up. Blood will be drawn, the nurse will administer the leuprolide or leuprolide placebo injection, and metformin or metformin placebo will be dispensed. At the final visit (week 12), participants will undergo a brief physical exam, and will then undergo a final euglycemic-hyperinsulinemic clamp.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: metformin, Drug: placebo injectionmetformin pill plus placebo injection |
| 2 | Experimental | Drug: leuprolide injection, Drug: placebo pillleuprolide injection plus placebo pill |
| 3 | Placebo comparator | Drug: placebo pill, Drug: placebo injectionplacebo pill plus placebo injection |
Who may qualify
- Ages
- 50 to 79 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Postmenopausal women aged 50-79 years with absence of menses for 12 months; for women 50-54 years, Follicle stimulating hormone>30 U/mL to confirm postmenopausal status
- At least one intact ovary
- Free testosterone and fasting insulin levels within required study parameters
- Willing to comply with all study-related procedures
- Capable of giving informed consent
Key exclusion criteria (23 listed)
- History of cancer requiring treatment within the past 5 years (exceptions may be made by investigator)
- Hospitalization for treatment of vascular disease in the past 6 months
- Uncontrolled hypertension
- Hospitalization for chronic obstructive pulmonary disease or asthma in the past 3 months
- Use of continuous oxygen at home
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metforminAlso: GlucophageInitiated on 500 mg daily and titrated up to 1000 mg twice a day during the first four weeks, remaining at that dose until 12 weeks | Drug | 1 |
| leuprolide injectionAlso: Lupron3.75 mg injection every 4 weeks (e.g. at baseline, 4, and 8 weeks) | Drug | 2 |
| placebo pillmatching pill twice a day for 12 weeks | Drug | 2, 3 |
| placebo injectionmatching injection every 4 weeks (e.g. baseline, 4, and 8 weeks) | Drug | 1, 3 |
Primary outcome
Percent Change in Free Testosterone (T)
Time frame: Baseline to 12 weeks
Percent change in free T by equilibrium dialysis between baseline and 12 weeks
Change in Insulin Sensitivity
Time frame: baseline and 12 weeks
Change in insulin sensitivity (mg/kg/min) calculated from hyperinsulinemic euglycemic clamp
7 secondary outcomes
Percent Change in Luteinizing Hormone (LH) From Baseline
Time frame: baseline and 12 weeks
Percent Change in Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR)
Time frame: baseline and 12 weeks
Percent Change in Low Density Lipoprotein (LDL)
Time frame: baseline and 12 weeks
Percent Change in Systolic Blood Pressure
Time frame: baseline and 12 weeks
Free T and IR in Women in Whom Metabolic Syndrome is Present vs. Absent
Time frame: baseline and 12 weeks
Dehydroepiandrosterone Sulfate (DHEA-S)
Time frame: baseline and 12 weeks
Body Mass Index (BMI)
Time frame: baseline and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11790215Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16;287(3):356-9. doi: 10.1001/jama.287.3.356.
- Background: PubMed 15353414Golden SH, Ding J, Szklo M, Schmidt MI, Duncan BB, Dobs A. Glucose and insulin components of the metabolic syndrome are associated with hyperandrogenism in postmenopausal women: the atherosclerosis risk in communities study. Am J Epidemiol. 2004 Sep 15;160(6):540-8. doi: 10.1093/aje/kwh250.
- Background: PubMed 8941471Larsson H, Ahren B. Androgen activity as a risk factor for impaired glucose tolerance in postmenopausal women. Diabetes Care. 1996 Dec;19(12):1399-403. doi: 10.2337/diacare.19.12.1399.
- Background: PubMed 11772901Oh JY, Barrett-Connor E, Wedick NM, Wingard DL; Rancho Bernardo Study. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care. 2002 Jan;25(1):55-60. doi: 10.2337/diacare.25.1.55.
- Individual participant dataSharing planned: No
Related trials for Insulin Resistance
Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
Not yet recruitingPhase 2
Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity
Insulin Resistance, Obesity
Recruiting
Effects of Urolithin A Supplementation on Glucose Metabolism in Healthy Adults 55 >= Years Old: A Randomized Triple-Masked Controlled Clinical Trial
Healthy Volunteer
Not yet recruitingPhase 2
Effects of Meal Macronutrients on Postprandial Lipids
Nephrotic Syndrome, Lipodystrophy
RecruitingObservational study
Food-i-Sense Analytics: Integrating AI Into Continuous Glucose Monitoring Data Analysis for Precision Nutrition.
Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), Artificial Intelligence Mobile Application
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne R. Cappola, MD, ScM principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing metformin and leuprolide injection in people with Insulin Resistance and Postmenopause, run by University of Pennsylvania 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 5 inclusion and 23 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 23 May 2019. 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 23 May 2019). 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?
Percent Change in Free Testosterone (T) (time frame: Baseline to 12 weeks). The study lists 2 primary outcomes in all. 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 NCT00123110, which also lists 4 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 23 May 2019.