Multiple Dose Effects of Hydrochlorothiazide and Isosorbide Mononitrate on Glucose Homeostasis (MK-0000-117)(Completed)
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Hydrochlorothiazide (HCTZ); Comparator: Placebo to HCTZ; Isosorbide mononitrate (ISMN); Comparator: Placebo to ISMN
Intervention description: HCTZ 50 mg (two 25 mg capsules) once daily for 4 weeks per treatment period.; Placebo to HCTZ two 0 mg capsules once daily for 4 weeks per treatment period; ISMN 60 mg extended release capsule once daily for 4 weeks per treatment period; Placebo to ISMN 0 mg capsule once daily for 4 weeks per treatment period
Intervention MeSH terms: Hydrochlorothiazide; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 64.0
Sex: All
Minimum age: 35 Years
Maximum age: 75 Years
Healthy volunteers: No

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