SMARTEST: Spermidine Anti-Hypertension Study
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Spermidine first 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
Placebo will be given orally as capsule (same size and weight as Spermidine capula)
Drug: Spermidine
Spermidine will be given orally as capsule (4mg/day)
|
| Other: Placebo first 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
Placebo will be given orally as capsule (same size and weight as Spermidine capula)
Drug: Spermidine
Spermidine will be given orally as capsule (4mg/day)
|
Outcome Measures
Primary Outcome Measures
- Systolic blood pressure in an ambulatory 24h blood pressure measurement [up to 24 weeks]
Patients will get RR recordings in an ambulatory setting
Secondary Outcome Measures
- Pulse wave velocity [up to 24 weeks]
recorded with the Mobil-O-Graph® PWA, I.E.M. GmbH, Stolberg, Germany
- diastolic blood pressure [up to 24 weeks]
recorded with the Mobil-O-Graph® PWA, I.E.M. GmbH, Stolberg, Germany
- mean blood pressure [up to 24 weeks]
recorded with the Mobil-O-Graph® PWA, I.E.M. GmbH, Stolberg, Germany
- central blood pressure [up to 24 weeks]
recorded with the Mobil-O-Graph® PWA, I.E.M. GmbH, Stolberg, Germany
- 6 minute walk test [up to 24 weeks]
tested at every visit
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical University of Graz | Graz | Austria | 8010 |
Sponsors and Collaborators
- Medical University of Graz
- University of Graz
- ETH Zurich
- Institut National de la Santé Et de la Recherche Médicale, France
- University Hospital Tuebingen
Investigators
- Principal Investigator: Dirk von Lewinski, MD, MUG
- Study Director: Simon Sedej, PhD, Medical University of Graz
- Study Director: Tobias Eisenberg, PhD, University of Graz
- Study Director: Mahmoud Abdellatif, MD, PhD, Medical University of Graz
Study Documents (Full-Text)
More Information
Publications
None provided.- 30-468 ex 17/18