Spermidine Anti-Hypertension Study (SMARTEST)

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.

Study Overview

• Status: Recruiting
• Conditions: Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Spermidine

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 Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dirk von Lewinski, MD; Phone Number: 80684 +43 316 385; Email: dirk.von-lewinski@medunigraz.at
• Study Contact Backup: Name: Markus Wallner, MD; Phone Number: 31262 +43 316 385; Email: markus.wallner@medunigraz.at

Study Locations

• Austria
  • Graz, Austria, 8010
    • Recruiting
    • Medical University of Graz
    • Contact: Dirk von Lewinski; Phone Number: +4331638580684; Email: dirk.von-lewinski@medunigraz.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; University Hospital Tuebingen; ETH Zurich; University of Graz
• 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

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2020
• Primary Completion (Anticipated): November 15, 2024
• Study Completion (Anticipated): November 15, 2024

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: May 25, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: 30-468 ex 17/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: individual data will only be shared after approval of the local EC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No