Clinical trial NCT04405388: Spermidine Anti-Hypertension Study
Official title: Spermidine Anti-Hypertension Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hypertension
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: University of Graz
name: ETH Zurich
name: Institut National de la Santé Et de la Recherche Médicale, France
name: University Hospital Tuebingen
First posted: 2020-05-28
Enrollment: 46
Sex: ALL
Minimum age (years): 19
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Eligibility 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

Primary outcomes:
measure: Systolic blood pressure in an ambulatory 24h blood pressure measurement
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Pulse wave velocity
timeFrame: up to 24 weeks
measure: diastolic blood pressure
timeFrame: up to 24 weeks
measure: mean blood pressure
timeFrame: up to 24 weeks
measure: central blood pressure
timeFrame: up to 24 weeks
measure: 6 minute walk test
timeFrame: up to 24 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
Study officials:
affiliation: MUG
name: Dirk von Lewinski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Graz
name: Simon Sedej, PhD
role: STUDY_DIRECTOR
affiliation: University of Graz
name: Tobias Eisenberg, PhD
role: STUDY_DIRECTOR
affiliation: Medical University of Graz
name: Mahmoud Abdellatif, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A, Tong M, Ruckenstuhl C, Dammbrueck C, Gross AS, Herbst V, Magnes C, Trausinger G, Narath S, Meinitzer A, Hu Z, Kirsch A, Eller K, Carmona-Gutierrez D, Buttner S, Pietrocola F, Knittelfelder O, Schrepfer E, Rockenfeller P, Simonini C, Rahn A, Horsch M, Moreth K, Beckers J, Fuchs H, Gailus-Durner V, Neff F, Janik D, Rathkolb B, Rozman J, de Angelis MH, Moustafa T, Haemmerle G, Mayr M, Willeit P, von Frieling-Salewsky M, Pieske B, Scorrano L, Pieber T, Pechlaner R, Willeit J, Sigrist SJ, Linke WA, Muhlfeld C, Sadoshima J, Dengjel J, Kiechl S, Kroemer G, Sedej S, Madeo F. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016 Dec;22(12):1428-1438. doi: 10.1038/nm.4222. Epub 2016 Nov 14.
citation: Wirth M, Benson G, Schwarz C, Kobe T, Grittner U, Schmitz D, Sigrist SJ, Bohlken J, Stekovic S, Madeo F, Floel A. The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial. Cortex. 2018 Dec;109:181-188. doi: 10.1016/j.cortex.2018.09.014. Epub 2018 Oct 4.