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

NCT ID: NCT00871871

Last Updated: 2015-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2010-03-31

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).

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part I, Placebo-HCTZ

Placebo in Period 1 followed by HCTZ in Period 2

Group Type: EXPERIMENTAL

Hydrochlorothiazide (HCTZ)

Intervention Type: DRUG

HCTZ 50 mg (two 25 mg capsules) once daily for 4 weeks per treatment period.

Comparator: Placebo to HCTZ

Intervention Type: DRUG

Placebo to HCTZ two 0 mg capsules once daily for 4 weeks per treatment period

Part I, HCTZ-Placebo

HCTZ in Period 1, followed by placebo in Period 2

Group Type: EXPERIMENTAL

Hydrochlorothiazide (HCTZ)

Intervention Type: DRUG

HCTZ 50 mg (two 25 mg capsules) once daily for 4 weeks per treatment period.

Comparator: Placebo to HCTZ

Intervention Type: DRUG

Placebo to HCTZ two 0 mg capsules once daily for 4 weeks per treatment period

Part II, Placebo-ISMN

Placebo in Period 1, followed by ISMN in Period 2

Group Type: EXPERIMENTAL

Isosorbide mononitrate (ISMN)

Intervention Type: DRUG

ISMN 60 mg extended release capsule once daily for 4 weeks per treatment period

Comparator: Placebo to ISMN

Intervention Type: DRUG

Placebo to ISMN 0 mg capsule once daily for 4 weeks per treatment period

Part II, ISMN-Placebo

ISMN in Period 1, followed by placebo in Period 2

Group Type: EXPERIMENTAL

Isosorbide mononitrate (ISMN)

Intervention Type: DRUG

ISMN 60 mg extended release capsule once daily for 4 weeks per treatment period

Comparator: Placebo to ISMN

Intervention Type: DRUG

Placebo to ISMN 0 mg capsule once daily for 4 weeks per treatment period

Interventions

Hydrochlorothiazide (HCTZ)

HCTZ 50 mg (two 25 mg capsules) once daily for 4 weeks per treatment period.

Intervention Type: DRUG

Comparator: Placebo to HCTZ

Placebo to HCTZ two 0 mg capsules once daily for 4 weeks per treatment period

Intervention Type: DRUG

Isosorbide mononitrate (ISMN)

ISMN 60 mg extended release capsule once daily for 4 weeks per treatment period

Intervention Type: DRUG

Comparator: Placebo to ISMN

Placebo to ISMN 0 mg capsule once daily for 4 weeks per treatment period

Intervention Type: DRUG

Other Intervention Names

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

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

2009_567

Identifier Type: -

Identifier Source: secondary_id

0000-117

Identifier Type: -

Identifier Source: org_study_id