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CompletedNCT01419535Updated Apr 14, 2021Results posted

Mifepristone Effects on Glucose Intolerance in Obese/Overweight Adults

A Phase 1/2 interventional study of Mifepristone and Placebo in Endocrine Disease and Diabetes, sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Completed at 1 site in United States. Open to participants aged 35 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-04-14.

Sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
19
Allocation
Randomized
Ages
35 Years to 70 Years
Sex
All
01

Study summary

Background:

  • Metabolic syndrome is a name given to a group of factors that tend to occur together. These risk factors include central obesity (extra weight around the middle of the body) and high blood pressure and blood sugar levels. They also include low levels of HDL ("good cholesterol") and high triglyceride levels. A person is said to have metabolic syndrome if they have three or more of the above risk factors. People with metabolic syndrome are at increased risk for type 2 diabetes, stroke, and heart disease.
  • Cortisol, a hormone produced by the adrenal glands, is an important regulator of metabolism. People with central obesity and metabolic syndrome may have higher than normal cortisol levels that the body cannot regulate properly. Abnormal cortisol levels may play an important role in metabolic syndrome. Mifepristone is a drug that blocks cortisol. Researchers are interested in studying its effects on metabolic syndrome.

Objectives:

  • To study the effects of short-term mifepristone treatment for metabolic syndrome.

Eligibility:

  • Men and Women between 35 and 70 years of age are overweight or obese, and have abnormal glucose and triglyceride levels.

Design:

  • Participants will be screened with a physical exam and medical history. They will also have blood and urine tests.
  • Participants will be admitted to the metabolic unit at the National Institutes of Health Clinical Center for the first 3 days of the study:
  • Day 1: Body measurements (height, weight, waist, hip, and neck) and blood pressure tests. Also, 24 hours of regular blood draws and 24-hour urine collection to monitor regular daily cortisol levels.
  • Day 2: Glucose/insulin infusion test to measure blood sugar levels.
  • Day 3: Infusion of cortisol-like compounds and then regular blood draws for about 3 hours to evaluate how cortisol is metabolized.
  • At the end of Day 3, participants will receive mifepristone or a look-alike capsule to take for 7 days at home.
  • After 7 days, participants will return to the metabolic unit to repeat the Day 1 and Day 2 study procedures. They will continue to take mifepristone.
  • One week after the second set of study tests, participants will return for a brief physical exam and blood tests.
  • The study procedures will be repeated after 6 to 8 weeks, with the other study drug.
Read the detailed description

The hormone cortisol is a key regulator of metabolism that influences the use of glucose (sugar) and fat as fuels. Persistently increased cortisol levels, as in Cushing s syndrome, lead to obesity, type 2 diabetes mellitus and lipid abnormalities including elevated triglyceride levels and low high-density lipoprotein (HDL) levels. These same disorders are also present in patients without Cushing s syndrome, suggesting that cortisol may be involved in their pathogenesis. Mifepristone is a cortisol-like drug that blocks cortisol action in the body. It can reverse lipid abnormalities, diabetes and obesity in Cushing s syndrome patients but its effects on these conditions have not been tested in patients without the syndrome.

The long-term aim of this clinical trial is to evaluate the ability of mifepristone to reverse or improve glucose intolerance, dyslipidemia, hypertension and weight gain. An initial 7-day prospective, randomized, placebo-controlled, crossover study is proposed here to look at the effect of short-term administration of oral mifepristone or placebo on glucose intolerance. Given that there are no human data available on the effect of mifepristone on insulin sensitivity, this will be a pilot study of 15 subjects. Data from this study will then be used to design a larger trial to evaluate long-term effects on blood pressure and weight, as well as glucose and triglyceride control.

Overweight or obese subjects with abnormal glucose tolerance will undergo each of the two treatments in a randomized order, including mifepristone by mouth and a look-alike inert tablet by mouth. Each treatment study will include two or three days of baseline tests that will be repeated after seven days of treatment. Treatments will be separated by at least six and no more than eight weeks. The tests will include blood drawing, urine collection, administration of glucose and insulin by vein, and a cortisol-like material to evaluate the metabolism of cortisol and a related hormone, corticosterone.

02

Conditions studied

  • Endocrine Disease
  • Diabetes

Keywords

  • Metabolism
  • Cortisol
  • Hypercortisolism
  • Glucose Intolerance
03

In context

Overweight

3,670 studies on the registry are indexed under Overweight; 849 are open to participants now.

This study's enrollment of 19 is below the median of 73 across 3,175 interventional studies indexed under Overweight.

Browse Overweight studies →

Lead sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is the lead sponsor of 416 studies on the registry; 25 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 10 (77%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
35 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Men and women 35 - 70 years of age

    1. Subjects will be overweight or obese, with body mass index (BMI) ranging from 25 - 37 kg/m2.

    2. Subjects will have either impaired fasting glucose (greater than or equal to 100 mg/dL) or a 2-hour glucose value greater than or equal to 140 mg/dl during an oral glucose tolerance test (OGTT).

      OR

      Mild diabetes defined as patients with a Hemoglobin A1C (HbA1C) less than or equal to 7% on no medications (diet-controlled) or on a stable dose of metformin and no other hypoglycemic agents for greater than or equal to 3 months before study entry.

    3. Willing and able to comply with study requirements.

Exclusion criteria

EXCLUSION CRITERIA:

  1. Pregnancy and lactation
  2. Diabetes requiring pharmacologic treatment. Diagnosis of diabetes will be based on the 2011 American Diabetes Association guidelines: HbA1C greater than or equal to 6.5%, fasting plasma glucose greater than or equal to 126 mg/dl, 2-hour glucose greater than or equal to 200 mg/dl during an OGTT, or a random blood glucose greater than or equal to 200 mg/dl along with classic symptoms of hyperglycemia (34)
  3. Uncontrolled hypertension (blood pressure greater than or equal to 180/110 mmHg)
  4. Current unstable medical conditions including clinically significant impaired cardiac function (Stage III and IV Cardiac failure), cardiac ischemia, severe respiratory insufficiency requiring oxygen therapy as assessed on history and/or physical exam
  5. Liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST) more than 3-times the upper normal limit
  6. Severe renal impairment (creatinine clearance \< 30 ml/min)
  7. Evidence of human immunodeficiency virus (HIV) based on history and physical examination and/or known positive HIV antibodies
  8. Evidence of hepatitis C based on history and physical examination and/or known positive hepatitis C (HCV) antibody
  9. History of hemorrhagic disorders or on anticoagulants
  10. History of endometrial cancer, endometrial hyperplasia, unexplained vaginal bleeding, or endometrial thickness greater than 6 mm
  11. Change in dose of lipid-lowering medications (including 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG Co-A) inhibitors , fibrates, niacin, ezetimibe, and over-the-counter fish oil supplements) within one month of study entry and during the study period
  12. Current administration of medications known to be strong CYP3A4 inhibitors including ketoconazole, itraconazole, and erythromycin
  13. Use of herbal supplements or grapefruit juice within 14 days of study drug initiation
  14. Use of medications or dietary supplements that inhibit or induce CYP3A4 activity within 14 days of study drug initiation
  15. Use of oral, injectable, or inhaled glucocorticoids or megestrol in the past six months
  16. Use of estrogen-containing hormone therapy
  17. Potential pseudocushing's states: depression or intake of > 2 alcoholic drinks a day. Subjects will be screened for depression using the well-validated physician health questionnaire-9 (PHQ-9) with a score cut-off of greater than or equal to 10 for moderate depression (35).
  18. Subjects who are actively dieting or are in a weight loss program
  19. Midnight salivary cortisol > 100 ng/dl on two separate occasions
  20. Untreated thyroid dysfunction (thyroid stimulating hormone and Free thyroxine (FT4) not within normal range). If abnormal on screening labs, they will be repeated to confirm that not due to lab error or non-thyroidal illness.
  21. Moderate to severe anemia (hemoglobin \< 10 g/dl)
  22. Blood donation of more than 500 ml within one month prior to study enrollment
  23. Subjects with a prolonged corrected Q-T interval (QTc) on electrocardiogram
  24. Unable to give informed consent
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
19 participants (actual)

Study arms

  • Experimental
    Mifepristone, then Placebo

    Participants first received Mifepristone 50mg tablet every six hours for nine days. After a washout period of no fewer than 6 but no more than 8 weeks, they then received Placebo tablet (matching mifepristone 50 mg) every six hours for nine days.

    Drug: Mifepristone · Drug: Placebo

  • Experimental
    Placebo, then Mifepristone

    Participants first received Placebo tablet (matching mifepristone 50 mg) every six hours for nine days. After a washout period of no fewer than 6 but no more than 8 weeks, they then received Mifepristone 50 mg tablet every six hours for nine days.

    Drug: Mifepristone · Drug: Placebo

Interventions

  • DrugMifepristone

    Mifepristone 50mg tablet by mouth every six hours for nine days.

    Also known as: 55245, 11β-[p-(Dimethylamino)phenyl]-17α-(1-propynyl)estra-4,9-dien-17β-ol-3-one

  • DrugPlacebo

    Placebo (matching mifepristone 50mg tablet) by mouth every six hours for nine days.

    Also known as: inert look-alike tablet

06

What researchers measure

Primary outcomes

  1. Change in Insulin Sensitivity Index

    insulin sensitivity index based on the effect of insulin on glucose during frequently sampled intravenous glucose tolerance test (FSIVGTT)

    Time frame: Nine days

Secondary outcomes

  1. Change in Fasting Plasma Glucose

    fasting plasma glucose after study agent compared to baseline

    Time frame: Nine days

  2. Change in Fasting Insulin Levels

    Fasting insulin after study agent administration compared to baseline

    Time frame: 9 days

  3. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

    HOMA-IR is an index of insulin resistance, measured as glucose in mmol/L x insulin in mIU/mL)/22.5. HOMA-IR \> 2.5 indicates insulin resistance.

    Time frame: 9 days

  4. Adipose-tissue Insulin Resistance Index (Adipo-IR)

    The adipose tissue insulin resistance index (Adipo-IR), a surrogate measure for fasting adipose-tissue insulin resistance, was calculated as the product of fasting insulin and fasting free fatty acids (FFA)

    Time frame: 9 days

  5. Adipose-tissue Insulin Sensitivity Index (Adipo-SI)

    The Adipo-SI was calculated as ratio of the slope of the linear decrease in natural log transformed FFA \[Ln (FFA) slope\] during the first 90 minutes of the FSIVGTT and the area under the curve (AUC) of insulin during that 90-minute period (AUC Insulin 0-90 min).

    Time frame: 9 days

07

Results

Posted Apr 14, 2021

Participant flow

Subjects were recruited to the study by advertisements and fliers. Sixty-three adults were evaluated at the single study site (the NIH Clinical Center) after providing informed consent. The first subject consented on November 11, 2011 and the final subject consented on April 16, 2015.

Participant flow — Overall Study
MilestoneMifepristone, Then PlaceboPlacebo, Then Mifepristone
Started910
Completed88
Not completed12
Withdrew: Could not maintain iv line11
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryChange in Insulin Sensitivity Index

insulin sensitivity index based on the effect of insulin on glucose during frequently sampled intravenous glucose tolerance test (FSIVGTT)

Time frame:
Nine days
Reported as:
Mean · min-1·μU·ml-1
Change in Insulin Sensitivity Index
min-1·μU·ml-1Post-mifepristonePost-placebo
Change in Insulin Sensitivity Index1.49 ± 1.171.41 ± 0.87
Statistical analysis
  • Post-mifepristone vs Post-placebo · ANOVA · p = 0.60Repeated measures were analyzed by repeated-measures ANOVA including treatment group, time, and treatment\*time interaction as factors.
SecondaryChange in Fasting Plasma Glucose

fasting plasma glucose after study agent compared to baseline

Time frame:
Nine days
Reported as:
Mean · mg/dL
Change in Fasting Plasma Glucose
mg/dLPost-mifepristonePost-placebo
Change in Fasting Plasma Glucose100.4 ± 5.3107.8 ± 15.7
Statistical analysis
  • Post-mifepristone vs Post-placebo · ANOVA · p = <0.001Repeated measures were analyzed by repeated-measures ANOVA including treatment group, time, and treatment\*time interaction as factors.
SecondaryChange in Fasting Insulin Levels

Fasting insulin after study agent administration compared to baseline

Time frame:
9 days
Reported as:
Mean · pmol/L
Change in Fasting Insulin Levels
pmol/LPost-mifepristonePost-placebo
Change in Fasting Insulin Levels95.6 ± 76.1142.8 ± 102.2
Statistical analysis
  • Post-mifepristone vs Post-placebo · ANOVA · p = <0.001Repeated measures were analyzed by repeated-measures ANOVA including treatment group, time, and treatment\*time interaction as factors.
SecondaryHomeostatic Model Assessment of Insulin Resistance (HOMA-IR)

HOMA-IR is an index of insulin resistance, measured as glucose in mmol/L x insulin in mIU/mL)/22.5. HOMA-IR \> 2.5 indicates insulin resistance.

Time frame:
9 days
Reported as:
Mean · units on a scale
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
units on a scalePost-mifepristonePost-placebo
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)3.58 ± 3.275.78 ± 4.92
Statistical analysis
  • Post-mifepristone vs Post-placebo · ANOVA · p = <0.001Repeated measures were analyzed by repeated-measures ANOVA including treatment group, time, and treatment\*time interaction as factors.
SecondaryAdipose-tissue Insulin Resistance Index (Adipo-IR)

The adipose tissue insulin resistance index (Adipo-IR), a surrogate measure for fasting adipose-tissue insulin resistance, was calculated as the product of fasting insulin and fasting free fatty acids (FFA)

Time frame:
9 days
Reported as:
Mean · mmol/l·μU/l
Adipose-tissue Insulin Resistance Index (Adipo-IR)
mmol/l·μU/lPost-mifepristonePost-placebo
Adipose-tissue Insulin Resistance Index (Adipo-IR)49.9 ± 45.965.5 ± 43.8
Statistical analysis
  • Post-mifepristone vs Post-placebo · ANOVA · p = 0.004Repeated measures were analyzed by repeated-measures ANOVA including treatment group, time, and treatment\*time interaction as factors.
SecondaryAdipose-tissue Insulin Sensitivity Index (Adipo-SI)

The Adipo-SI was calculated as ratio of the slope of the linear decrease in natural log transformed FFA \[Ln (FFA) slope\] during the first 90 minutes of the FSIVGTT and the area under the curve (AUC) of insulin during that 90-minute period (AUC Insulin 0-90 min).

Time frame:
9 days
Reported as:
Mean · ln(mmol /uU/mL*min)*10^8
Adipose-tissue Insulin Sensitivity Index (Adipo-SI)
ln(mmol /uU/mL*min)*10^8Post-mifepristonePost-placebo
Adipose-tissue Insulin Sensitivity Index (Adipo-SI)61.7 ± 32.942.8 ± 23.9
Statistical analysis
  • Post-mifepristone vs Post-placebo · ANOVA · p = 0.002Repeated measures were analyzed by repeated-measures ANOVA including treatment group, time, and treatment\*time interaction as factors.

Adverse events

Collected over Subjects returned for safety labs and discussion of any adverse events on approximately day 19 and day 33 after discontinuation of study agents.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Post-mifepristone0/16 (0%)0/16 (0%)0/16 (0%)
Post-placebo0/16 (0%)0/16 (0%)2/16 (12.5%)
Most frequent other events
Most frequent other events
EventPost-mifepristonePost-placebo
abnormal blood chemistryHepatobiliary disorders0/162/16

Baseline characteristics

Age, Continuous
Age, Continuous(years)Mifepristone, Then PlaceboPlacebo, Then MifepristoneTotal
Mean56.6 ± 6.552.8 ± 8.954.7 ± 7.8
Sex: Female, Male
Sex: Female, Male(Participants)Mifepristone, Then PlaceboPlacebo, Then MifepristoneTotal
Female437
Male459
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Mifepristone, Then PlaceboPlacebo, Then MifepristoneTotal
Hispanic or Latino101
Not Hispanic or Latino7815
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Mifepristone, Then PlaceboPlacebo, Then MifepristoneTotal
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American347
White437
More than one race000
Unknown or Not Reported011
Region of Enrollment
Region of Enrollment(participants)Mifepristone, Then PlaceboPlacebo, Then MifepristoneTotal
United States8816
Weight
Weight(kg)Mifepristone, Then PlaceboPlacebo, Then MifepristoneTotal
Mean92.8 ± 15.8102 ± 15.997.2 ± 16.0
Body mass index
Body mass index(kg/M^2)Mifepristone, Then PlaceboPlacebo, Then MifepristoneTotal
Mean30.8 ± 4.1234.0 ± 2.3732.4 ± 4.12
systolic blood pressure
systolic blood pressure(mmHg)Mifepristone, Then PlaceboPlacebo, Then MifepristoneTotal
Mean124 ± 16.1133 ± 10.5128 ± 13.9

10 further baseline measures are reported on the registry.

08

Study locations

1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike
    Bethesda, Maryland 20892, United States
09

References and documents

Publications

  • Pivonello R, Faggiano A, Lombardi G, Colao A. The metabolic syndrome and cardiovascular risk in Cushing's syndrome. Endocrinol Metab Clin North Am. 2005 Jun;34(2):327-39, viii. doi: 10.1016/j.ecl.2005.01.010. PubMed 15850845 ↗
  • Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab. 2009 Aug;94(8):2692-701. doi: 10.1210/jc.2009-0370. Epub 2009 May 26. PubMed 19470627 ↗
  • Pasquali R, Vicennati V, Cacciari M, Pagotto U. The hypothalamic-pituitary-adrenal axis activity in obesity and the metabolic syndrome. Ann N Y Acad Sci. 2006 Nov;1083:111-28. doi: 10.1196/annals.1367.009. PubMed 17148736 ↗
  • Gubbi S, Muniyappa R, Sharma ST, Grewal S, McGlotten R, Nieman LK. Mifepristone Improves Adipose Tissue Insulin Sensitivity in Insulin Resistant Individuals. J Clin Endocrinol Metab. 2021 Apr 23;106(5):1501-1515. doi: 10.1210/clinem/dgab046. PubMed 33507248 ↗

Study documents

  • Protocol and statistical analysis plan · Nov 16, 2017
  • Informed consent form · Nov 29, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Upon reasonable request, individual participant data will be shared with other investigators

Supporting information: Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 14, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01419535
Lead sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Responsible party
Sponsor
First posted
Aug 18, 2011
Start date
Nov 29, 2011
Primary completion
Nov 24, 2015
Completion
Nov 24, 2015
Results posted
Apr 14, 2021
Last update
Apr 14, 2021

Study contacts

Lynnette K Nieman, M.D.
principal investigator · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Oversight

FDA-regulated drug
Yes
View the source record on ClinicalTrials.gov ↗

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