Spermidine Anti-Hypertension Study (SMARTEST)

Medical University of Graz

Status and phase: Enrolling; Phase 3

Conditions: Hypertension

Treatments: Drug: Spermidine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04405388

30-468 ex 17/18

Details and patient eligibility

About

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.

Full 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

Enrollment: 46 estimated patients

Sex: All

Ages: 19 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

46 participants in 2 patient groups

Spermidine first

Other group

Description:

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.

Treatment:

Drug: Placebo

Drug: Spermidine

Placebo first

Other group

Description:

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.

Treatment:

Drug: Placebo

Drug: Spermidine