Reducing Circulating Sphingolipid Levels to Optimise Cardiometabolic Health - The SphingoFIT Trial

NCT06024291 | Completed

• 1 other identifier: EKNZ 2023-01345
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effects of an 8-week supervised high-intensity interval training (HIIT) program (vs. physical activity recommendations according to current guidelines) on a comprehensive panel of circulating sphingolipids in middle-aged females and males at elevated cardiometabolic risk.

Conditions

Overweight and Obesity; Dyslipidemias; Blood Pressure; Cardiovascular Diseases; Metabolic Disease

Outcome Measures

Primary Outcomes (1)

• Concentration of circulating Cer16:0, Cer18:0, Cer24:0 and Cer24:1

  Quantifying the changes in plasma level of the four sphingolipid species included in the ceramide-based scores (Cer16:0, Cer18:0, Cer24:0 and Cer24:1) following the 8-week HIIT programme (vs. physical activity recommendation).

  At baseline and after the 8-week intervention

Secondary Outcomes (5)

• Concentration of the other circulating sphingolipid species to be targeted

  At baseline and after the 8-week intervention

• Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

  At baseline and after the 8-week intervention

• Peak oxygen uptake (VO2peak)

  At baseline and after the 8-week intervention

• Retinal microvascular diameters

  At baseline and after the 8-week intervention

• Brachial flow-mediated dilatation (FMD)

  At baseline and after the 8-week intervention

Study Arms (2)

HIIT group

EXPERIMENTAL

The exercise intervention will consist of a supervised HIIT (two walking- and one indoor cycling-based session weekly), starting with a habituation week at an intensity of 75% of the maximal heart rate (HRmax). In the following seven weeks, the participants will perform a HIIT based on the following protocol and for a total duration of 45 min per session: warm-up for 10 min at 60%-70% HRmax followed by a high-intensity interval consisting of 4×4 min at 80%-95% HRmax with 3 min of active recovery at 60%-70% HRmax and a 10 min cool-down at 60%-70% HRmax. Heart rate will be monitored during training by Garmin HRM-Dual heart rate sensors combined with Garmin Forerunner 45S watches. Exercise scientists motivate the participants during the intervals and will control each participant's heart rate during and after every training session.

Other: 8-week HIIT programme

Physical activity recommendation group

ACTIVE COMPARATOR

Asking physically inactive participants to maintain their inactive habits may not reflect realistic conditions and is no longer considered the best option in a randomised controlled exercise intervention. Indeed, most participants will be aware of the positive effects of PA - or will become aware of them during an exercise intervention study. Further, denying an exercise intervention to participants who would have benefited from it (for instance, participants at risk of cardiometabolic diseases) might be ethically questionable. In accordance with current practices, control group participants will be informed about the World Health Organization physical activity guidelines at the beginning of the study.

Other: Physical activity recommendation

Interventions

8-week HIIT programme OTHER

See arm description

HIIT group

Physical activity recommendation OTHER

See arm description

Physical activity recommendation group

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• female or male sex,
• aged between 40 and 60 years,
• body mass index between 25.0 and 34.9 kg/m2,
• sedentary lifestyle, defined as not meeting the WHO guidelines on PA, i.e., at least 150 minutes of moderate-intensity aerobic PA per week as well as muscle-strengthening activities on two or more days per week,
• medical clearance for HIIT by a study physician (including vital sign evaluation, clinical examination, resting and exercise ECG),
• informed consent as documented by signature.

You may not qualify if:

• known pregnancy or breastfeeding,
• any current exercise-limiting musculoskeletal conditions of the lower limbs,
• any known current or chronic conditions limiting exhaustive exercise,
• known diabetes mellitus of any type,
• dyslipidaemia, if pharmaceutically treated,
• arterial hypertension ≥160/100 mmHg, pharmaceutically treated or not,
• any other known cardiovascular disease,
• known NASH,
• known macular degeneration, glaucoma, or high intraocular pressure (≥20 mm Hg),
• particular diet (vegetarian, vegan, lactose-free, gluten-free, or FODMAP-low diet (ferment-able oligosaccharides, disaccharides, monosaccharides, and polyols),
• intake of glucagon-like peptide-1 analogues, orlistat or any weight-loss drug,
• inability to follow the procedures of the study, e.g., due to linguistic or cognitive problems,
• concomitant involvement in another interventional trial or participation in another interventional trial in the last four weeks.

Sponsors & Collaborators

• University of Basel: lead
• University of Lausanne: collaborator
• Technical University of Munich: collaborator

Study Sites (1)

Department of Sport, Exercise and Health, University of Basel

Basel, Canton of Basel-City, 4052, Switzerland

Location

Related Publications (5)

• Choi RH, Tatum SM, Symons JD, Summers SA, Holland WL. Ceramides and other sphingolipids as drivers of cardiovascular disease. Nat Rev Cardiol. 2021 Oct;18(10):701-711. doi: 10.1038/s41569-021-00536-1. Epub 2021 Mar 26.

  PMID: 33772258 BACKGROUND

• Laaksonen R, Ekroos K, Sysi-Aho M, Hilvo M, Vihervaara T, Kauhanen D, Suoniemi M, Hurme R, Marz W, Scharnagl H, Stojakovic T, Vlachopoulou E, Lokki ML, Nieminen MS, Klingenberg R, Matter CM, Hornemann T, Juni P, Rodondi N, Raber L, Windecker S, Gencer B, Pedersen ER, Tell GS, Nygard O, Mach F, Sinisalo J, Luscher TF. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol. Eur Heart J. 2016 Jul 1;37(25):1967-76. doi: 10.1093/eurheartj/ehw148. Epub 2016 Apr 28.

  PMID: 27125947 BACKGROUND

• Tippetts TS, Holland WL, Summers SA. Cholesterol - the devil you know; ceramide - the devil you don't. Trends Pharmacol Sci. 2021 Dec;42(12):1082-1095. doi: 10.1016/j.tips.2021.10.001. Epub 2021 Nov 5.

  PMID: 34750017 BACKGROUND

• Carrard J, Angst T, Weber N, Bienvenue J, Infanger D, Streese L, Hinrichs T, Croci I, Schmied C, Gallart-Ayala H, Hochsmann C, Koehler K, Hanssen H, Ivanisevic J, Schmidt-Trucksass A. Investigating the circulating sphingolipidome response to a single high-intensity interval training session within healthy females and males in their twenties (SphingoHIIT): Protocol for a randomised controlled trial. F1000Res. 2023 Aug 18;11:1565. doi: 10.12688/f1000research.128978.3. eCollection 2022.

  PMID: 37533665 BACKGROUND

• Carrard J, Hofer M, Prechtl L, Fleischlin E, Huber M, Gallart-Ayala H, Teav T, Infanger D, Hochsmann C, Koehler K, Hinrichs T, Hanssen H, Ivanisevic J, Schmidt-Trucksass A. Effect of an eight-week high-intensity interval training programme on circulating sphingolipid levels in middle-aged adults at elevated cardiometabolic risk (SphingoFIT)-Protocol for a randomised controlled exercise trial. PLoS One. 2024 May 8;19(5):e0302477. doi: 10.1371/journal.pone.0302477. eCollection 2024.

  PMID: 38717997 DERIVED

MeSH Terms

Conditions

Overweight; Obesity; Dyslipidemias; Cardiovascular Diseases; Metabolic Diseases

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lipid Metabolism Disorders

Study Officials

• Arno Schmidt-Trucksäss, Prof, MD, MA

  Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: As the randomisation will take place after the baseline examination, participants, exercise scientists, and physicians supervising the intervention will be blinded for group allocation at baseline but not post-intervention.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Postdoctoral researcher, Principal investigator

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: September 6, 2023
• Study Start: September 15, 2023
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)