Clinical trial NCT00871871: Multiple Dose Effects of Hydrochlorothiazide and Isosorbide Mononitrate on Glucose Homeostasis (MK-0000-117)(Completed)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-03-30
Enrollment: 64
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Glucose Tolerance (IGT)
timeFrame: 90 -120 minutes post-dose
measure: Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Fasting Glucose (IFG)
timeFrame: 90 -120 minutes post-dose
measure: Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants Who Had Normal Glucose Tolerance (NGT)
timeFrame: 90 -120 minutes post-dose
measure: Part II: Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady-state
timeFrame: 90 -120 minutes post-dose
Secondary outcomes:
measure: Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Glucose Tolerant (IGT)
timeFrame: 90 -120 minutes post-dose
measure: Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Fasting Glucose (IFG)
timeFrame: 90 -120 minutes post-dose
measure: Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Normal Glucose Tolerant (NGT)
timeFrame: 90 -120 minutes post-dose
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References: