Vascular Dysfunction in Human Obesity Hypertension

NCT01983462 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 201307779
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to test the effects of blocking sympathetic nerve activity with a drug called clonidine on blood vessel function and muscle nerve activity in adults who are obese and have high blood pressure. The cohort of subjects will consist of 69 healthy young men and women age 18-79 years who are obese, defined as a body mass index \> or = to 30 kg/m2, who have untreated systolic hypertension (systolic blood pressure \> or = to 130 - \<180 mmHg- average of at least 3 measurements 2 min apart after 10 min seated resting position). These 69 subjects will then be randomized to 3 treatment arms: clonidine (0.1 mg/day), hydrochlorothiazide (25 mg/day) or placebo for 4 weeks in years 1 and 2. All tablets will be encapsulated by to look identical. Subjects will randomly (1:1:1) receive one of the following combinations in a double-blind, placebo-controlled design:

1. 1.Oral clonidine (0.1 mg twice/day)
2. 2.Oral hydrochlorothiazide (12.5 mg twice/day)
3. 3.Oral placebo

Conditions

Obesity; Prehypertension; Hypertension

Keywords

Prehypertension; Hypertension; Obese; Sympathetic Nervous System; renin-angiotensin system; Endothelial function

Outcome Measures

Primary Outcomes (1)

• Aortic Stiffness

  Carotid-femoral pulse wave velocity (PWV)

  4 weeks

Secondary Outcomes (1)

• 24 Hour Average Systolic Blood Pressure

  4 weeks

Study Arms (3)

Clonidine

EXPERIMENTAL

Oral 0.2 mg/day (0.1 mg bid)for 4 weeks

Drug: Clonidine

Hydrochlorothiazide

ACTIVE COMPARATOR

Oral, 12.5 mg/day qd, 4 weeks

Drug: Hydrochlorothiazide

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Clonidine DRUG

Also known as: Catapress

Clonidine

Hydrochlorothiazide DRUG

Hydrochlorothiazide

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
• Systolic blood pressure \>/= 130 mmHg and \<180 mmHg
• Age is \> or = 18 and \< or = 79 years of age
• Weight stable (+/- 5 lbs) for the previous 3 months
• Healthy, as determined by health history questionnaire, blood chemistries, 12-lead ECG
• Blood chemistries indicative of normal renal (creatinine \<2.0 mg/dl), liver (\<3 times upper limit for ALT, AST), and thyroid function (TSH between 0.4 - 5.0 mU/L)
• If currently receiving treatment with or taking any of the following supplements, be willing and able to discontinue taking them for 2 weeks prior and throughout the treatment period: Vitamin C, E or other multivitamins containing vitamin C or E; or omega-3 fatty acids.
• No history of cardiovascular disease (e.g., heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy), Type 1 or Type 2 diabetes, or peripheral arterial disease
• Non-smokers, defined as no history of smoking or no smoking for at least the past 1 year
• Normal resting 12-lead ECG (no evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter)

You may not qualify if:

• Systolic blood pressure \>/=180 mmHg or diastolic blood pressure \>110 mmHg
• History of cardiovascular disease such as heart angioplasty/stent or bypass surgery, myocardial infarction, stroke, heart failure with or without left ventricular ejection fraction \<40%, cardiomyopathy, valvular heart disease, cardiomyopathy, heart transplantation, Type 2 and Type 1 diabetes
• Smoking or history of smoking within past one year
• History of gastric ulcers, bleeding disorders, dyspepsia, severe gastroesophageal reflux disease (GERD), or metabolic acidosis
• History of chronic obstructive pulmonary disease (COPD)
• Abnormal resting 12-lead ECG (e.g., evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter)
• Serious neurologic disorders including seizures
• History of renal failure, dialysis or kidney transplant
• Serum creatinine \> 2.0 mg/dL, or hepatic enzyme (ALT/AST) concentrations \> 3 times the upper limit of normal
• History of HIV infection, hepatic cirrhosis, other preexisting liver disease, or positive HIV, Hepatitis B or C test at screening.
• Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
• History of recent chicken pox, shingles or influenza (ie., risk of Reye's syndrome)
• Recent flu-like symptoms within the past 2 weeks
• Pregnant or breastfeeding at screening, or planning to become pregnant (self or partner) at any time during the study. A urinary pregnancy test will be done on all females. If test is positive, the subject will be excluded.
• Women with history of hormone replacement therapy within the past 6 months

Sponsors & Collaborators

• Gary L. Pierce: lead
• American Heart Association: collaborator

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52240, United States

Location

MeSH Terms

Conditions

Obesity; Prehypertension; Hypertension

Interventions

Clonidine; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Gary Pierce, PhD
• Organization: University of Iowa

gary-pierce@uiowa.edu

3193359487

Study Officials

• Gary L Pierce, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 30, 2013
• First Posted: November 14, 2013
• Study Start: October 1, 2013
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: April 14, 2023
• Results First Posted: April 14, 2023

Record last verified: 2023-03

Locations

US (1)