Multiple Dose Effects of Hydrochlorothiazide and Isosorbide Mononitrate on Glucose Homeostasis

Condition(s) targeted: Hypertension

Intervention: non-product or non-Merck product (Drug); Comparator: Placebo to HCTZ (Drug); Comparator: Isosorbide mononitrate (ISMN) (Drug); Comparator: Placebo to ISMN (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Merck

Official(s) and/or principal investigator(s):
Medical Monitor, Study Director, Affiliation: Merck

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).

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 design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Pharmacodynamics Study

Primary outcome:

Part I: Decrease in insulin secretion at steady-state compared to placebo

Part II: Increase in the ratio of whole body glucose disposal to plasma insulin at steady-state

Secondary outcome: Part I: Decrease in the ratio of whole body glucose disposal to plasma insulin at steady state

Minimum age: 35 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Female patients must be post-menopausal

- Patient has a BMI of at least 29 kg/m^2

- Patient's weight has been stable over the past 3 months

- Patient has never been treated for hypertension or is diagnosed with hypertension

taking up to 2 anti-hypertensive medications

- Patient is willing to stop hypertension treatment for 14 days prior to randomization

and throughout the study

- Patient does not have a history of diabetes

- Patient is in good health with the exception of hypertension

- Patient has no history of abnormal heart rhythms

- Part I only: Patient is willing to comply with high potassium/low sodium diet for the

duration of the study

- Patient is willing to avoid strenuous physical activity during the study

- Patient is a 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

- Patient agrees to refrain from consuming alcohol and caffeine during in-patient

periods and to limit consumption at all other times during the study

- Patient 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:

- Patient has a history of any illness that may make their participation in the study

unsafe or confuse the study results

- Patient is taking spironolactone or eplerenone

- Patient cannot refrain from using any prescription or non-prescription drugs during

the study

- Patient is on a weight loss program and is not in the maintenance phase

- Patient started a weight loss drug within 8 weeks of the first study visit

- Patient consumes excessive amounts of alcohol or caffeine

- Patient has had major surgery, donated or lost 1 unit of blood within 4 weeks of the

first study visit

- Patient has a history of multiple and/or severe allergies to drugs or food

- Patient is dehydrated

MSD (Pty) LTD South Africa, Midrand, Gauteng 1685, South Africa; Recruiting
Beverley Cowper, Phone: 27 11 655-3036

Starting date: March 2009
Ending date: November 2009
Last updated: October 8, 2009