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Multiple Dose Effects of Hydrochlorothiazide and Isosorbide Mononitrate on Glucose Homeostasis (MK-0000-117)(Completed)

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ClinicalTrials.gov Identifier: NCT00871871
Recruitment Status : Completed
First Posted : March 30, 2009
Results First Posted : September 22, 2011
Last Update Posted : July 28, 2015
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

March 27, 2009
March 30, 2009
February 22, 2011
September 22, 2011
July 28, 2015
March 2009
February 2010   (Final data collection date for primary outcome measure)
  • Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Glucose Tolerance (IGT) [ Time Frame: 90 -120 minutes post-dose ]
    Steady state was defined as 90-120 minutes post-dose. IGT was defined as a 2 hour plasma glucose >= 140 and <= 199 mg/dL during a 75g oral glucose tolerance test at screening.
  • Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Fasting Glucose (IFG) [ Time Frame: 90 -120 minutes post-dose ]
    Steady state was defined as 90-120 minutes post-dose. IFG was defined as fasting plasma glucose (FPG) between 100 and 125 mg/dL at screening.
  • Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants Who Had Normal Glucose Tolerance (NGT) [ Time Frame: 90 -120 minutes post-dose ]
    Steady state was defined as 90-120 minutes post-dose. NGT participants (FPG <100 mg/dL & 2 hour plasma glucose (PG) <140 mg/dL during a 75g oral glucose tolerance test (OGTT) at screening) were neither Impaired Glucose Tolerant (IGT) nor Impaired Fasting Glucose (IFG). IGT was defined as a 2 hour plasma glucose >= 140 and <= 199 mg/dL during a 75g oral glucose tolerance test at screening. IFG was defined as FPG between 100 and 125 mg/dL at screening.
  • Part II: Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady-state [ Time Frame: 90 -120 minutes post-dose ]
    Steady state was defined as 90-120 minutes post-dose. The ratio was the quantity of glucose disposed by the body per kg body weight per minute at steady state divided by the approximate steady state plasma insulin concentration. The approximate steady state plasma insulin concentration was estimated by the time-weighted average of the insulin concentration measured at 10 minute intervals in which time = 90, 100, 110, and 120 minutes.
  • Part I: Decrease in insulin secretion at steady-state compared to placebo [ Time Frame: 4 weeks ]
  • Part II: Increase in the ratio of whole body glucose disposal to plasma insulin at steady-state [ Time Frame: 4 weeks ]
Complete list of historical versions of study NCT00871871 on ClinicalTrials.gov Archive Site
  • Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Glucose Tolerant (IGT) [ Time Frame: 90 -120 minutes post-dose ]
    Steady state was defined as 90-120 minutes post-dose. The ratio was the quantity of glucose disposed by the body per kg body weight per minute at steady state divided by the approximate steady state plasma insulin concentration. The approximate steady state plasma insulin concentration was estimated by the time-weighted average of the insulin concentration measured at 10 minute intervals in which time = 90, 100, 110, and 120 minutes. IGT was defined as a 2 hour plasma glucose >= 140 and <= 199 mg/dL during a 75g oral glucose tolerance test at screening.
  • Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Fasting Glucose (IFG) [ Time Frame: 90 -120 minutes post-dose ]
    Steady state was defined as 90-120 minutes post-dose. The ratio was the quantity of glucose disposed by the body per kg body weight per minute at steady state divided by the approximate steady state plasma insulin concentration. The approximate steady state plasma insulin concentration was estimated by the time-weighted average of the insulin concentration measured at 10 minute intervals in which time = 90, 100, 110, and 120 minutes. IFG was defined as fasting plasma glucose (FPG) between 100 and 125 mg/dL at screening.
  • Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Normal Glucose Tolerant (NGT) [ Time Frame: 90 -120 minutes post-dose ]
    Steady state was defined as 90-120 minutes post-dose. The ratio was the measure of the quantity of glucose disposed per unit of plasma insulin concentration (PIC). Approximate PIC was estimated by the time-weighted average of the insulin concentration measured at 10 minute intervals, time = 90, 100, 110, and 120 minutes. NGT participants (FPG <100 mg/dL & 2 hour PG <140 mg/dL during a 75g OGTT at screening) were neither IGT nor IFG at screening. IGT - defined as a 2 hour PG >= 140 and <= 199 mg/dL during a 75g OGTT at screening. IFG - defined as FPG between 100 and 125 mg/dL at screening.
Part I: Decrease in the ratio of whole body glucose disposal to plasma insulin at steady state [ Time Frame: 4 weeks ]
Not Provided
Not Provided
 
Multiple Dose Effects of Hydrochlorothiazide and Isosorbide Mononitrate on Glucose Homeostasis (MK-0000-117)(Completed)
A Randomized, Double-Blind, Placebo-Controlled, 2-Part Study to Evaluate the Multiple Dose Effects of Hydrochlorothiazide and Isosorbide Mononitrate on Glucose Homeostasis in Obese Patients With Hypertension
This study will measure and compare changes in insulin production and sensitivity using the hyperglycemic clamp technique in obese patients with impaired glucose tolerance and hypertension treated with placebo, isosorbide mononitrate (ISMN) or hydrochlorothiazide (HCTZ).
Not Provided
Interventional
Phase 1
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Hypertension
  • Drug: Hydrochlorothiazide (HCTZ)
    HCTZ 50 mg (two 25 mg capsules) once daily for 4 weeks per treatment period.
    Other Name: HCTZ
  • Drug: Comparator: Placebo to HCTZ
    Placebo to HCTZ two 0 mg capsules once daily for 4 weeks per treatment period
  • Drug: Isosorbide mononitrate (ISMN)
    ISMN 60 mg extended release capsule once daily for 4 weeks per treatment period
  • Drug: Comparator: Placebo to ISMN
    Placebo to ISMN 0 mg capsule once daily for 4 weeks per treatment period
  • Experimental: Part I, Placebo-HCTZ
    Placebo in Period 1 followed by HCTZ in Period 2
    Interventions:
    • Drug: Hydrochlorothiazide (HCTZ)
    • Drug: Comparator: Placebo to HCTZ
  • Experimental: Part I, HCTZ-Placebo
    HCTZ in Period 1, followed by placebo in Period 2
    Interventions:
    • Drug: Hydrochlorothiazide (HCTZ)
    • Drug: Comparator: Placebo to HCTZ
  • Experimental: Part II, Placebo-ISMN
    Placebo in Period 1, followed by ISMN in Period 2
    Interventions:
    • Drug: Isosorbide mononitrate (ISMN)
    • Drug: Comparator: Placebo to ISMN
  • Experimental: Part II, ISMN-Placebo
    ISMN in Period 1, followed by placebo in Period 2
    Interventions:
    • Drug: Isosorbide mononitrate (ISMN)
    • Drug: Comparator: Placebo to ISMN
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
64
60
March 2010
February 2010   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Female participants must be post-menopausal
  • Body Mass Index (BMI) of at least 29 kg/m^2
  • Weight has been stable over the past 3 months
  • Has never been treated for hypertension or is diagnosed with hypertension taking up to 2 anti-hypertensive medications
  • Willing to stop hypertension treatment for 14 days prior to randomization and throughout the study
  • Does not have a history of diabetes
  • In good health with the exception of hypertension
  • No history of abnormal heart rhythms
  • Part I only: willing to comply with high potassium/low sodium diet for the duration of the study
  • Willing to avoid strenuous physical activity during the study
  • Nonsmoker and/or has not used nicotine for at least 3 months and agrees to refrain from use of tobacco-containing products throughout the study
  • Agrees to refrain from consuming alcohol and caffeine during in-patient periods and to limit consumption at all other times during the study
  • Agrees not to consume grapefruit, grapefruit products, and citrus, apple, and pineapple juices 2 weeks prior to administration of the first dose of study drug

Exclusion Criteria:

  • History of any illness that may make their participation in the study unsafe or confuse the study results
  • Taking spironolactone or eplerenone
  • Cannot refrain from using any prescription or non-prescription drugs during the study
  • On a weight loss program and is not in the maintenance phase
  • Started a weight loss drug within 8 weeks of the first study visit
  • Consumes excessive amounts of alcohol or caffeine
  • Has had major surgery, donated or lost 1 unit of blood within 4 weeks of the first study visit
  • History of multiple and/or severe allergies to drugs or food
  • Is dehydrated
Sexes Eligible for Study: All
35 Years to 75 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
South Africa
 
NCT00871871
0000-117
2009_567
No
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP