sPERMIdine supplemenTation on Metabolic, Neuronal and Cardiovascular Response to Exercise TRAINING (PERMIT_EX)

The Effect of sPERMIdine supplemenTation on the Metabolic, Neuronal and Cardiovascular Response to Exercise TRAINING in Patients With Heart Failure With Preserved Ejection Fraction

This study explores whether spermidine supplementation improves the metabolic, neurological-cognitive and cardiovascular response to structured exercise training in patients with heart failure with preserved ejection fraction. The investigators aim to show that a faster adaptation to exercise may improve long term adherence to a more active lifestyle.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure, Diastolic
• Intervention / Treatment: Dietary supplement: spermidineLife; Dietary supplement: Placebo

Detailed Description

Heart failure with preserved ejection fraction is the largest unmet need in medicine. Exercise training is a pivotal lifestyle intervention which has been shown to have beneficial effects with regards to metabolic, neurological-cognitive and cardiovascular outcomes in these patients. Yet, not every patients responds equally fast to an exercise training intervention. This trial explores whether the supplementation of spermidine can increase the response to a structured aerobic exercise training. The investigators will recruit 30 patients who will either receive a spermidine supplement or a placebo. The study participants are invited for a first follow-up visit after four weeks. The exercise intervention starts at week 5 and continues for 12 weeks. Hence, overall there are three visits (baseline, week four and week twelve).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marcus Dörr, MD; Phone Number: +4938348680500; Email: marcus.doerr@med.uni-greifswald.de
• Study Contact Backup: Name: Martin Bahls, PhD; Phone Number: +4938348680500; Email: martin.bahls@med.uni-greifswald.de

Study Locations

• Germany
  • Greifswald, Germany, 17489
    • Recruiting
    • Cardiovascular examination center of the University Medicine Greifswald
    • Contact: Martin Bahls, Ph.D.; Phone Number: +49 3834 8680500; Email: martin.bahls@uni-greifswald.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diastolic heart failure (E/e' > 8, left ventricular ejection fraction (LVEF) => 50 %, dyspnea)

Exclusion Criteria:

• nutritional supplements with polyamines
• acute myo-, endo- or pericarditis
• aortic valve stenosis (2nd degree)
• cardiomyopathy or severe left ventricular hypertrophy (Interventricular septal end diastolic thickness or posterior wall thickness > 17 mm)
• AV block (second degree)
• pulmonary hypertension
• thromboembolic event in the last six months
• anemia
• infection (with fever) within the last four weeks
• cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Spermidine supplementation; Study participants are provided with spermidine supplementation	Dietary supplement: spermidineLife; dietary supplement that is made of natural wheat germ extract with high spermidine content
Placebo Comparator: Placebo supplementation; Study participants are provided with a placebo supplementation	Dietary supplement: Placebo; dietary supplement that is made of cellulose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiorespiratory exercise capacity	Change in cardiorespiratory exercise capacity (VO2peak) in ml/min/kg before and after of exercise training	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diastolic function	Change in diastolic function based on echocardiography (E/e')	16 weeks
Microvascular function	Reactive hyperemia index assessed using EndoPat	16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple-Choice Vocabulary Intelligence Test (MWT-B)	Multiple-Choice Vocabulary Intelligence Test: Measure: total number of correctly checked lines. Final outcome: IQ (standard value and percentile rank)	16 weeks
Mnemonic Similarity Task (MST)	Mnemonic Similarity Task (MST). % of correctly answered tasks (0 - 100 %). final outcome: D - Prime	16 weeks
Verbal Learning and Memory Test (VLMT)	Verbal Learning and Memory Test (VLMT) % of correctly answered tasks (0 - 100 %). final outcome: D - Prime	16 weeks
Digit Span test battery for attention testing	Digit Span test battery for attention testing; from 0 to 8, Score: maximum number of digits that were correctly remembered after 3 erros the test ends. direction of the task (forward or backwards), the longest sequence successfully reached and passed, and the total number of attempts	16 weeks
brain magnetic resonance imaging (MRI) - T1	brain magnetic resonance imaging (MRI) T1 to assess cortical brain structure pre and post intervention	16 weeks
brain magnetic resonance imaging (MRI) - FLAIR	brain magnetic resonance imaging (MRI) - FLAIR to assess white matter hyperintensities pre and post intervention	16 weeks
brain magnetic resonance imaging (MRI) - DTI	brain magnetic resonance imaging (MRI) - DTI to assess fractional anisotropy and fiber tracking pre and post intervention	16 weeks
brain magnetic resonance imaging (MRI) - resting state fMRI	brain magnetic resonance imaging (MRI) resting state fMRI to assess brain network connectivity pre and post intervention	16 weeks

Collaborators and Investigators

• Sponsor: University Medicine Greifswald

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Exercise; Spermidine
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic
• Other Study ID Numbers: PERMIT-HGW-DZHK40

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Our ethics approval does not allow to share IPD for this trial.

Drug and device information, study documents

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