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.

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.

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

Individual Participant Data will not be shared to maintain anonymity and confidentiality of the participants

Double (Participant, Investigator)