Angiotensin 1-7 in Obesity Hypertension

NCT03604289 | Terminated Early Phase 1 FDA Drug

• 2 other identifiers: STUDY0000817018POST33960087
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if the investigational drug angiotensin-(1-7) improves cardiovascular health in patients with obesity and high blood pressure.

Conditions

Obesity; Hypertension

Keywords

angiotensin-1-7

Outcome Measures

Primary Outcomes (1)

• Change in brachial artery diameter with reactive hyperemia

  A blood pressure cuff will be inflated to a suprasystolic pressure for 5 minutes then deflated. Brachial artery diameter will be measured continuously before, during, and after cuff inflation using duplex ultrasound.

  15 minutes including baseline, cuff inflation, and reactive hyperemia

Secondary Outcomes (5)

• Heart Rate Variability

  30 minutes

• Circulating catecholamines

  5 minutes

• Change in coronary blood velocity to the cold pressor test

  20 minutes

• Change in systolic and diastolic blood pressure to the cold pressor test

  20 minutes

• Change in muscle sympathetic nerve activity to the cold pressor test

  20 minutes

Study Arms (2)

Angiotensin-(1-7)

EXPERIMENTAL

Participants receive intravenous angiotensin-(1-7) at one study visit for 100 minutes total. Angiotensin-(1-7) will be given in escalating doses of 2ng/kg/min, 4ng/kg/min, and 8ng/kg/min. Each of these doses will be infused for 10 minutes. Following the dose escalation, angiotensin-(1-7) will be given at 8ng/kg/min for an additional 70 minutes. Infusion rates will be calculated for each patient based on body mass.

Drug: Angiotensin-(1-7)

Saline

PLACEBO COMPARATOR

Participants receive intravenous saline at one study visit for 100 minutes total. The volume of saline will match the volume of angiotensin-(1-7) infused. Infusion rates will be calculated for each patient based on body mass. Saline will be given in escalating doses for 10 minutes each and then held for 70 minutes at the highest dose.

Drug: Saline

Interventions

Angiotensin-(1-7) DRUG

This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.

Also known as: Angiotensin I/II (1-7) Acetate

Angiotensin-(1-7)

Saline DRUG

Saline will be used as the placebo comparator

Also known as: Normal saline, 0.9% sodium chloride

Saline

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women of all races
• Capable of giving informed consent
• Age 18-60 years
• Body mass index (BMI) between 30-40 kg/m2
• Hypertension defined as two or more seated blood pressure readings \>130/80 mmHg or use of anti-hypertensive medications
• Satisfactory history and physical exam

You may not qualify if:

• Age ≤ 17 or ≥ 61 years
• Pregnant or nursing women
• Decisional impairment
• Prisoners
• Alcohol or drug abuse
• Current smokers
• Highly trained athletes
• Subjects with \>5% weight change in the past 3 months
• Evidence of type I or type II diabetes (fasting glucose \> 126 mg/dL or use of anti-diabetic medications)
• History of serious cardiovascular disease (e.g. myocardial infarction within 6 months, symptomatic coronary artery disease, presence of angina pectoris, significant arrhythmia, congestive heart failure, deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, hypertrophic cardiomyopathy) or cerebrovascular disease (e.g. cerebral hemorrhage, stroke, transient Ischemic attack).
• History or presence of immunological or hematological disorders
• Impaired hepatic function (AST or ALT levels \>2 times upper limit of normal range)
• Impaired renal function (serum creatinine \>2.0 mg/dl)
• Anemia
• Treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors

Sponsors & Collaborators

• Amy Arnold: lead
• American Heart Association: collaborator

Study Sites (1)

Penn State College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Obesity; Hypertension

Interventions

angiotensin I (1-7); Acetates; Sodium Chloride; Saline Solution

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)

Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Amy C Arnold, Ph.D.

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 19, 2018
• First Posted: July 27, 2018
• Study Start: April 1, 2019
• Primary Completion: May 3, 2023
• Study Completion: June 3, 2023
• Last Updated: June 10, 2024

Record last verified: 2024-06

Locations

US (1)