Sympathoinhibition as a Preferred Second Line Treatment of Obesity Related Hypertension

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Sympathoinhibition as a Preferred Second Line Treatment of Obesity Related Hypertension

Conditions
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Obesity, Hypertension

Intervention / Treatment
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* Drug: Moxonidine 0.4 MG
* Drug: Amlodipine 5mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double blind cross over study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1<br>Moxonidine 0.4mg/daily | Drug: Moxonidine 0.4 MG<br>* 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.<br>Drug: Amlodipine 5mg<br>* 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.<br>|
| Experimental: Phase 2<br>Amlodipine 5mg | Drug: Moxonidine 0.4 MG<br>* 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.<br>Drug: Amlodipine 5mg<br>* 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.<br>|

What is the study measuring?
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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 |