CompletedNCT00871871Updated Jul 28, 2015Results posted

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

A Phase 1 interventional study of Hydrochlorothiazide (HCTZ) and Comparator: Placebo to HCTZ in Hypertension, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 35 Years to 75 Years. Per ClinicalTrials.gov, last updated 2015-07-28.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 64
Allocation: Randomized
Ages: 35 Years to 75 Years
Sex: All

Study 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 studied

Hypertension

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Hypertension 6,689

In context

Hypertension

6,689 studies on the registry are indexed under Hypertension; 965 are open to participants now.

This study's enrollment of 64 is below the median of 90 across 4,995 interventional studies indexed under Hypertension.

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Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 35 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Double (Participant, Investigator)
Enrollment: 64 participants (actual)

Study arms

Experimental
Part I, Placebo-HCTZ
Placebo in Period 1 followed by HCTZ in Period 2
Drug: Hydrochlorothiazide (HCTZ) · Drug: Comparator: Placebo to HCTZ
Experimental
Part I, HCTZ-Placebo
HCTZ in Period 1, followed by placebo in Period 2
Drug: Hydrochlorothiazide (HCTZ) · Drug: Comparator: Placebo to HCTZ
Experimental
Part II, Placebo-ISMN
Placebo in Period 1, followed by ISMN in Period 2
Drug: Isosorbide mononitrate (ISMN) · Drug: Comparator: Placebo to ISMN
Experimental
Part II, ISMN-Placebo
ISMN in Period 1, followed by placebo in Period 2
Drug: Isosorbide mononitrate (ISMN) · Drug: Comparator: Placebo to ISMN

Interventions

DrugHydrochlorothiazide (HCTZ)
HCTZ 50 mg (two 25 mg capsules) once daily for 4 weeks per treatment period.
Also known as: HCTZ
DrugComparator: Placebo to HCTZ
Placebo to HCTZ two 0 mg capsules once daily for 4 weeks per treatment period
DrugIsosorbide mononitrate (ISMN)
ISMN 60 mg extended release capsule once daily for 4 weeks per treatment period
DrugComparator: Placebo to ISMN
Placebo to ISMN 0 mg capsule once daily for 4 weeks per treatment period

What researchers measure

Primary outcomes

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Glucose Tolerance (IGT)
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.
Time frame: 90 -120 minutes post-dose
Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Fasting Glucose (IFG)
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.
Time frame: 90 -120 minutes post-dose
Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants Who Had Normal Glucose Tolerance (NGT)
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.
Time frame: 90 -120 minutes post-dose
Part II: Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady-state
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.
Time frame: 90 -120 minutes post-dose

Secondary outcomes

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Glucose Tolerant (IGT)
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.
Time frame: 90 -120 minutes post-dose
Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Fasting Glucose (IFG)
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.
Time frame: 90 -120 minutes post-dose
Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Normal Glucose Tolerant (NGT)
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.
Time frame: 90 -120 minutes post-dose

Results

Posted Sep 22, 2011

Participant flow

Part I

Participant flow — Part I
Milestone	HCTZ First, Then HCTZ Placebo	HCTZ Placebo First, Then HCTZ
Started	18	18
Completed	15	15
Not completed	3	3
Withdrew: Adverse event	0	2
Withdrew: Withdrawal by subject	3	0
Withdrew: Laboratory abnormality	0	1

Part II

Participant flow — Part II
Milestone	ISMN First, Then ISMN Placebo	ISMN Placebo First, Then ISMN
Started	13	15
Completed	9	11
Not completed	4	4
Withdrew: Lack of efficacy	1	0
Withdrew: Withdrawal by subject	2	1
Withdrew: Adverse event	1	2
Withdrew: Protocol violation	0	1

Outcome measures

PrimaryPart I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Glucose Tolerance (IGT)

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.

Time frame:: 90 -120 minutes post-dose
Reported as:: Least squares mean · ng/minute

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Glucose Tolerance (IGT)
ng/minute	Hydrochlorothiazide (HCTZ)	Hydrochlorothiazide (HCTZ) Placebo
Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Glucose Tolerance (IGT)	3.44 ± 1.03	3.55 ± 1.03

Statistical analysis

Hydrochlorothiazide (HCTZ) vs Hydrochlorothiazide (HCTZ) Placebo · ANCOVA · p = 0.067 (one-sided, alpha = 0.05) · Least squares mean difference: -0.10 · 90% CI -0.22 to 0.01

PrimaryPart I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Fasting Glucose (IFG)

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.

Time frame:: 90 -120 minutes post-dose
Reported as:: Least squares mean · ng/minute

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Fasting Glucose (IFG)
ng/minute	Hydrochlorothiazide (HCTZ)	Hydrochlorothiazide (HCTZ) Placebo
Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Fasting Glucose (IFG)	5.60 ± 1.45	4.50 ± 0.95

Statistical analysis

Hydrochlorothiazide (HCTZ) vs Hydrochlorothiazide (HCTZ) Placebo · ANCOVA · p = >0.500 · Least squares mean difference: 1.10 · 90% CI 0.86 to 1.34

SecondaryPart I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Glucose Tolerant (IGT)

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.

Time frame:: 90 -120 minutes post-dose
Reported as:: Least squares mean · (mg/kg/minute)/(µIU/mL)

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Glucose Tolerant (IGT)
(mg/kg/minute)/(µIU/mL)	Hydrochlorothiazide (HCTZ)	Hydrochlorothiazide (HCTZ) Placebo
Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Glucose Tolerant (IGT)	0.061 ± 0.044	0.045 ± 0.041

Statistical analysis

Hydrochlorothiazide (HCTZ) vs Hydrochlorothiazide (HCTZ) Placebo · ANOVA · p = 0.130 (one-sided, alpha = 0.05) · Least squares mean difference: 0.016 · 90% CI -0.012 to 0.044

PrimaryPart I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants Who Had Normal Glucose Tolerance (NGT)

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.

Time frame:: 90 -120 minutes post-dose
Reported as:: Least squares mean · ng/minute

Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants Who Had Normal Glucose Tolerance (NGT)
ng/minute	Hydrochlorothiazide (HCTZ)	Hydrochlorothiazide (HCTZ) Placebo
Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants Who Had Normal Glucose Tolerance (NGT)	5.54 ± 2.15	5.01 ± 1.63

Statistical analysis

Hydrochlorothiazide (HCTZ) vs Hydrochlorothiazide (HCTZ) Placebo · ANCOVA · p = >0.500 · Least squares mean difference: 0.54 · 90% CI 0.40 to 0.67

PrimaryPart II: Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady-state

Time frame:: 90 -120 minutes post-dose
Reported as:: Least squares mean · (mg/kg/minute)/(µIU/mL)

Part II: Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady-state
(mg/kg/minute)/(µIU/mL)	Isosorbide Mononitrate (ISMN)	Isosorbide Mononitrate (ISMN) Placebo
Part II: Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady-state	0.040 ± 0.027	0.044 ± 0.041

Statistical analysis

Isosorbide Mononitrate (ISMN) vs Isosorbide Mononitrate (ISMN) Placebo · ANOVA · p = 0.342 (one-sided, alpha = 0.05) · Least squares mean difference: 0.004 · 90% CI -0.023 to 0.014

SecondaryPart I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Fasting Glucose (IFG)

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.

Time frame:: 90 -120 minutes post-dose
Reported as:: Least squares mean · (mg/kg/minute)/(µIU/mL)

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Fasting Glucose (IFG)
(mg/kg/minute)/(µIU/mL)	Hydrochlorothiazide (HCTZ)	Hydrochlorothiazide (HCTZ) Placebo
Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Fasting Glucose (IFG)	0.038 ± 0.019	0.037 ± 0.109

Statistical analysis

Hydrochlorothiazide (HCTZ) vs Hydrochlorothiazide (HCTZ) Placebo · ANOVA · p = >0.500 · Least squares mean difference: 0.0016 · 90% CI -0.008 to 0.011

SecondaryPart I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Normal Glucose Tolerant (NGT)

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.

Time frame:: 90 -120 minutes post-dose
Reported as:: Least squares mean · (mg/kg/minute)/(µIU/mL)

Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Normal Glucose Tolerant (NGT)
(mg/kg/minute)/(µIU/mL)	Hydrochlorothiazide (HCTZ)	Hydrochlorothiazide (HCTZ) Placebo
Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Normal Glucose Tolerant (NGT)	0.045 ± 0.028	0.042 ± 0.024

Statistical analysis

Hydrochlorothiazide (HCTZ) vs Hydrochlorothiazide (HCTZ) Placebo · ANOVA · p = >0.500 · Least squares mean difference: 0.003 · 90% CI -0.003 to 0.010

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
HCTZ	—	0/36 (0%)	29/36 (80.6%)
HCTZ Placebo	—	0/36 (0%)	25/36 (69.4%)
ISMN	—	0/28 (0%)	26/28 (92.9%)
ISMN Placebo	—	0/28 (0%)	17/28 (60.7%)

Most frequent other events

Showing 10 of 72

Most frequent other events
Event	HCTZ	HCTZ Placebo	ISMN	ISMN Placebo
HeadacheNervous system disorders	11/36	12/36	26/28	14/28
Muscle spasmsMusculoskeletal and connective tissue disorders	4/36	5/36	5/28	1/28
NauseaGastrointestinal disorders	3/36	3/36	5/28	0/28
Musculoskeletal painMusculoskeletal and connective tissue disorders	0/36	1/36	4/28	2/28
NasopharyngitisInfections and infestations	5/36	3/36	0/28	0/28
Blood potassium decreasedInvestigations	4/36	0/36	0/28	0/28
DizzinessNervous system disorders	4/36	2/36	3/28	1/28
PollakiuriaRenal and urinary disorders	4/36	1/36	0/28	0/28
DiarrhoeaGastrointestinal disorders	1/36	0/36	1/28	3/28
Back painMusculoskeletal and connective tissue disorders	3/36	0/36	0/28	1/28

Baseline characteristics

Age, Continuous
Age, Continuous(years)	All Part I Participants	All Part II Participants	Total
Mean	57 (35 to 72)	54 (37 to 73)	55 (35 to 73)

Sex: Female, Male
Sex: Female, Male(Participants)	All Part I Participants	All Part II Participants	Total
Female	20	13	33
Male	16	15	31

Study locations

No study locations are listed for this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 28, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00871871
Lead sponsor: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Mar 30, 2009
Start date: Mar 2009
Primary completion: Feb 2010
Completion: Mar 2010
Results posted: Sep 22, 2011
Last update: Jul 28, 2015

Study contacts

Medical Monitor

study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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

Study summary

Conditions studied

Browse trials for

In context

Hypertension

Lead sponsor

Who can participate

✓Inclusion criteria

✕Exclusion criteria

Study design

Study arms

Interventions

What researchers measure

Primary outcomes

Secondary outcomes

Results

Participant flow

Outcome measures

Adverse events

Baseline characteristics

Study locations

Updates

Registry details

Key details

Study contacts

Oversight

Not currently enrolling

Follow this study

Discussion

Other studies in this condition

Other studies from this sponsor

Inclusion criteria

Exclusion criteria