Spermidine Anti-Hypertension Study

NCT ID: NCT04405388

Last Updated: 2023-01-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-25
• Study Completion Date: 2024-11-15

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

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: OTHER

Placebo

Intervention Type: DRUG

Placebo will be given orally as capsule (same size and weight as Spermidine capula)

Spermidine

Intervention Type: DRUG

Spermidine will be given orally as capsule (4mg/day)

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.

Group Type: OTHER

Placebo

Intervention Type: DRUG

Placebo will be given orally as capsule (same size and weight as Spermidine capula)

Spermidine

Intervention Type: DRUG

Spermidine will be given orally as capsule (4mg/day)

Interventions

Placebo

Placebo will be given orally as capsule (same size and weight as Spermidine capula)

Intervention Type: DRUG

Spermidine

Spermidine will be given orally as capsule (4mg/day)

Intervention Type: DRUG

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Graz

OTHER

Sponsor Role: collaborator

ETH Zurich

OTHER

Sponsor Role: collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: collaborator

Medical University of Graz

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dirk von Lewinski, MD

Role: PRINCIPAL_INVESTIGATOR

MUG

Simon Sedej, PhD

Role: STUDY_DIRECTOR

Medical University of Graz

Tobias Eisenberg, PhD

Role: STUDY_DIRECTOR

University of Graz

Mahmoud Abdellatif, MD, PhD

Role: STUDY_DIRECTOR

Medical University of Graz

Locations

Medical University of Graz

Graz, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Dirk von Lewinski, MD

Role: CONTACT

dirk.von-lewinski@medunigraz.at

+43 316 385 ext. 80684

Markus Wallner, MD

Role: CONTACT

markus.wallner@medunigraz.at

+43 316 385 ext. 31262

Facility Contacts

Dirk von Lewinski

Role: primary

dirk.von-lewinski@medunigraz.at

+4331638580684

References

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.

Reference Type: RESULT

PMID: 27841876 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30388439 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

30-468 ex 17/18

Identifier Type: -

Identifier Source: org_study_id