Spermidine Anti-Hypertension Study

Study Overview
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Brief Summary
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The impact of daily spermidine application on arterial blood pressure and other secondary parameters will be evaluated in a double-blind single center 46 patients cross-over study.

Detailed Description
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Arterial hypertension is a central risk factor for cardiovascular disease, major cardiovascular events and mortality. Treatment of arterial hypertension necessitates lifestyle modifications, but often also requires medical intervention. In most cases, a combination of two or more anti-hypertensive drugs is recommended and necessary for reaching the target blood pressure levels. Hypotheses / research questions/objectives Spermidine potentiates the blood pressure lowering effect of standard anti-hypertensive medications, particularly when a combination of at least two first-line drugs (as recommended by the European Society of Cardiology guidelines) has not resulted in sufficient and adequate blood pressure control. Approach/methods Spermidine Anti-Hypertension Study (SMARTEST) is a prospective, randomized and double-blind placebo-controlled single-centre trial with a balanced 2x2 crossover design, where 46 medically pre-treated hypertensive patients will be subsequently treated with spermidine and placebo (each for eight weeks) in two arms of opposite treatment sequence. A washout period of four weeks will separate the two intervention periods in both arms. Patients will undergo physical examination, ECG (electrocardiogram), echocardiography, and blood draws at four time points coinciding with the baseline and termination of each treatment at: 0, 8, 12, and 20 weeks of/after recruitment at the Department of Cardiology, Medical University of Graz. In addition, 24-hour ambulatory blood pressure (24-h BP) monitoring (BPM; Mobil-O-Graph®) and on-site blood pressure will be obtained (the device will be sent back to the hospital the following day) at these time points. A 6-minute walk test (6MWT) will be performed at every visit. Spermidine will be administered orally as an approved dietary supplement (spermidine-rich wheat germ extract) at a dose of 4 mg spermidine per day for eight weeks. The primary outcome will be arterial systolic blood pressure at 24h BPM. Further secondary outcomes/safety outcomes will be: 24-h BP: analysis of systolic, diastolic and mean arterial blood pressures and pulse wave analysis; on site ambulatory blood pressure; 6 minute walk test distance (difference in meters); laboratory analysis; ECG - standard parameters; Echocardiography: standard parameters as well as strain analysis

Official Title
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Spermidine Anti-Hypertension Study

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Placebo
* Drug: Spermidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide signed and dated informed consent form Persistant arterial hypertension with systolic blood pressure above 150 mmHg during hospitalisation and the day of randomisation Stable anti-hypertensive medication with at least two guideline-recommended anti-hypertensive drugs Exclusion Criteria: Systolic blood pressure ≥180mmHg on the day of randomisation Spermidine intolerance Significant renal impairment defined as glomerular filtration rate < 45ml/min Insulin-dependent diabetes mellitus (IDDM) Wheat allergy or gluten intolerance Life expectancy of less than 12 months Participation in another clinical trial

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 99 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Spermidine first<br>First treatment period (8 weeks) will be 4 mg spermidine per day orally. Afterwards 4 weeks of wash-out followed by 8 weeks of placebo treatment. | Drug: Placebo<br>* Placebo will be given orally as capsule (same size and weight as Spermidine capula)<br>Drug: Spermidine<br>* Spermidine will be given orally as capsule (4mg/day)<br>|
| Other: Placebo first<br>First treatment period (8 weeks) will be placebo. Afterwards 4 weeks of wash-out followed by 8 weeks of 4 mg spermidine per day orally. | Drug: Placebo<br>* Placebo will be given orally as capsule (same size and weight as Spermidine capula)<br>Drug: Spermidine<br>* Spermidine will be given orally as capsule (4mg/day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure in an ambulatory 24h blood pressure measurement | Patients will get RR recordings in an ambulatory setting | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulse wave velocity | recorded with the Mobil-O-Graph® PWA, I.E.M. GmbH, Stolberg, Germany | up to 24 weeks | 
| diastolic blood pressure | recorded with the Mobil-O-Graph® PWA, I.E.M. GmbH, Stolberg, Germany | up to 24 weeks | 
| mean blood pressure | recorded with the Mobil-O-Graph® PWA, I.E.M. GmbH, Stolberg, Germany | up to 24 weeks | 
| central blood pressure | recorded with the Mobil-O-Graph® PWA, I.E.M. GmbH, Stolberg, Germany | up to 24 weeks | 
| 6 minute walk test | tested at every visit | up to 24 weeks |