Sympathoinhibition as a Preferred Second Line Treatment of Obesity Related Hypertension (OHT)

This study is designed to investigate whether sympathoinhibition with moxonidine could provide added metabolic benefit compared to the second line therapy in the current guidelines.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Obesity
• Intervention / Treatment: Drug: Moxonidine 0.4 MG; Drug: Amlodipine 5mg

Detailed Description

This is a randomised, double-blind, cross-over study. Participants will be randomly assigned to receive either moxonidine 0.4mg daily or amlodipine 5mg and will later receive the alternate treatment.

Comprehensive testing will occur after each 12 week treatment phase and will include assessment of muscle sympathetic nerve activity, gut microbiome analysis and metabolic markers.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Revathy Carnagarin, MD; Phone Number: +61 8 92240316; Email: revathy.carnagarin@uwa.edu.au

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6155
      • Recruiting
      • Dobney Hypertension Centre
      • Contact: Markus Schlaich; Phone Number: +61 8 92240390; Email: markus.schlaich@uwa.edu.au
      • Contact: Revathy Carnagarin; Phone Number: +61 8 92240316; Email: revathy.carnagarin@uwa.edu.au
      • Sub-Investigator: Revathy Carnagarin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 25 -70 years
• (Body Mass Index) BMI≥30kg/m2
• Currently weight stable (+/- 3% in previous 6-12 months and not on any specific exercise or dietary program)
• Elevated clinic systolic (Blood Pressure) BP ≥135 or diastolic BP ≥85mmHg,
• on ACE inhibitor for at least 6 weeks prior to baseline assessment

Exclusion Criteria:

• Grade 2-3 hypertension (systolic office BP >160, diastolic office BP >100 mmHg)
• Secondary causes of hypertension
• CKD (Chronic kidney disease) stage 4-5 {(estimated glomerular filtration) eGFR<30ml/min}
• Heart failure NYHA (New York Heart Association) class II-IV
• Recent CV (cardiovascular) event (acute myocardial infarction, acute coronary syndrome, stroke or transient ischaemic attack within the previous six months) unstable psychiatric condition
• medication such as corticosteroids, several antidepressants and antipsychotics
• Female participants of childbearing potential must have a negative pregnancy test prior to treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Phase 1; Moxonidine 0.4mg/daily	Drug: Moxonidine 0.4 MG; Participants will be randomly assigned to receive moxonidine 0.4mg/daily and will later receive the alternate treatment. As the study is double blind neither the participant nor the study personnel will be aware of which treatment is currently being tested to avoid any effect this may have on the results. The two 12-week treatment phases will be separated by a 6-week wash out (drug-free) period.; Drug: Amlodipine 5mg; Participants will be randomly assigned to receive amlodipine 5mg and will later receive the alternate treatment. As the study is double blind neither the participant nor the study personnel will be aware of which treatment is currently being tested to avoid any effect this may have on the results. The two 12-week treatment phases will be separated by a 6-week wash out (drug-free) period.
EXPERIMENTAL: Phase 2; Amlodipine 5mg	Drug: Moxonidine 0.4 MG; Participants will be randomly assigned to receive moxonidine 0.4mg/daily and will later receive the alternate treatment. As the study is double blind neither the participant nor the study personnel will be aware of which treatment is currently being tested to avoid any effect this may have on the results. The two 12-week treatment phases will be separated by a 6-week wash out (drug-free) period.; Drug: Amlodipine 5mg; Participants will be randomly assigned to receive amlodipine 5mg and will later receive the alternate treatment. As the study is double blind neither the participant nor the study personnel will be aware of which treatment is currently being tested to avoid any effect this may have on the results. The two 12-week treatment phases will be separated by a 6-week wash out (drug-free) period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	Both Systolic and diastolic blood pressure assessed by office and ambulatory blood pressure monitoring	30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood glucose levels	Changes in glycemic control through oral glucose tolerance test	30 weeks
Gut microbiota profile	Change in gut microbiota assessed by short chain fatty acid	30 weeks
Lipid levels in blood	change in triglyceride, HDL and LDL levels in blood	30 weeks

Collaborators and Investigators

• Sponsor: Royal Perth Hospital
• Collaborators: The University of Western Australia
• Investigators: Principal Investigator: Markus Schlaich, MD, University of Western Australia and Royal Perth Hospital

Publications and helpful links

General Publications

• Carnagarin R, Gregory C, Azzam O, Hillis GS, Schultz C, Watts GF, Bell D, Matthews V, Schlaich MP. The Role of Sympatho-Inhibition in Combination Treatment of Obesity-Related Hypertension. Curr Hypertens Rep. 2017 Oct 28;19(12):99. doi: 10.1007/s11906-017-0795-1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 24, 2015
• Primary Completion (ANTICIPATED): February 24, 2024
• Study Completion (ANTICIPATED): June 24, 2024

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (ACTUAL): July 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hypertension; Obesity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine; Moxonidine
• Other Study ID Numbers: RA-4-1-7565

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data will not be shared to maintain anonymity and confidentiality of the participants

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No