Spermidine Anti-Hypertension Study
Spermidine Anti-Hypertension Study
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.
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
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