An Exercise and Lifestyle Programme for Adults With Vascular Ehlers-Danlos Syndrome: A Feasibility Study

Co-Producing and Piloting an Exercise-Based Lifestyle Intervention for Individuals With Vascular Ehlers-Danlos Syndrome (vEDS): A Mixed-Methods Feasibility Study

Vascular Ehlers-Danlos syndrome (vEDS) is a rare, life-threatening connective tissue disorder. People with vEDS have often been advised to limit physical activity, yet the safety and feasibility of structured exercise in this group is poorly understood. This study works with people with vEDS, their families and clinicians to co-design a safe, tailored physical activity programme, then tests it in a 12-week randomised feasibility study comparing the programme with usual care. The aim is to find out whether the intervention and the trial procedures are safe, acceptable and practical, in order to inform a future full-scale trial. Outcomes focus on recruitment, retention, adherence, acceptability and safety, alongside exploratory measures of physical function, quality of life and microvascular health.

Study Overview

• Status: Not yet recruiting
• Conditions: Vascular Ehlers Danlos Syndrome
• Intervention / Treatment: Behavioral: Co-designed exercise-based lifestyle intervention

Detailed Description

This is a mixed-methods feasibility study delivered across four phases. Phase 1 uses qualitative interviews with people with vEDS, family members and clinicians to understand experiences of physical activity and decision-making under uncertain clinical guidance. Phase 2 uses co-production focus groups to design the exercise-based lifestyle intervention. Phase 3 is a 12-week randomised feasibility trial in which adults with vEDS are randomised to the co-produced intervention or to usual care, assessing feasibility outcomes (recruitment, retention, adherence, data completeness, acceptability and safety) and exploratory clinical measures. Phase 4 uses post-intervention interviews to explore participant experiences and refine the intervention. The registered trial corresponds to the Phase 3 randomised feasibility component; the qualitative phases provide the development and evaluation context.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ian Thistlewood; Phone Number: +447939953194; Email: i.thistlewood@shu.ac.uk
• Study Contact Backup: Name: Markos Klonizakis; Email: m.klonizakis@shu.ac.uk

Study Locations

• United Kingdom
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2BP
      • Sheffield Hallam University
      • Contact: Markos Klonizakis; Email: m.klonizakis@shu.ac.uk
      • Contact: Ian Thistlewood; Phone Number: 07939953194; Email: i.thistlewood@shu.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 years or older
• Confirmed diagnosis of vascular Ehlers-Danlos syndrome (vEDS)
• Living in the UK
• Able to provide informed consent
• Medically stable, defined as: no arterial dissection, rupture, or other major vEDS-related vascular event within the preceding 6 months; no recent hospitalisation for vEDS complications; and blood pressure considered controlled by their treating clinician
• Medical clearance from their treating clinician
• Not pregnant at the time of enrolment

Exclusion Criteria:

• Major vEDS-related vascular event (arterial dissection or rupture) within the previous 6 months
• Recent hospitalisation for vEDS complications
• Blood pressure not controlled by treating clinician
• Pregnancy at enrolment (participants who become pregnant during the intervention are withdrawn from the exercise component but may continue follow-up data collection if they wish)
• Unable to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Participants receive a 12-week co-produced, remotely supervised, low-intensity and low-impact exercise-based lifestyle intervention, tailored to individual capacity, with weekly remote monitoring.	Behavioral: Co-designed exercise-based lifestyle intervention; A 12-week individually tailored exercise-based lifestyle programme, co-produced with people with vEDS, delivered remotely with supervision and weekly monitoring. Comprises low-intensity, low-impact aerobic and functional activity progressed to individual capacity, with behavioural support to encourage sustained physical activity.
No Intervention: Usual Care; Participants continue standard NHS medical care and any lifestyle advice from their treating clinicians, with no study intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	Proportion of eligible participants who consent to take part, expressed as a monthly recruitment rate.	From study start through completion of recruitment, up to 12 months
Retention rate	Proportion of randomised participants completing the 12-week intervention (progression target ≥80%)	12 weeks
Adherence	Proportion of prescribed exercise sessions completed (target ≥60%), assessed by session completion records and device-based monitoring (step count and heart rate via ActiGraph accelerometer	Over the 12-week intervention period
Data completeness	Proportion of participants completing outcome measures at baseline and 12 weeks (target ≥75%)	Baseline and 12 weeks
Acceptability	Acceptability assessed via a questionnaire informed by the Theoretical Framework of Acceptability (seven constructs, 5-point Likert scale), supplemented by post-intervention interviews	12 weeks
Adverse events and serious adverse events	Number, type and severity of adverse events and serious adverse events, reviewed by the independent Data Safety Committee.	Throughout the 12-week intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue	FACIT-Fatigue Scale (Functional Assessment of Chronic Illness Therapy - Fatigue); score range 0-52; higher scores indicate less fatigue (better outcome)	Baseline and 12 weeks
Anxiety and depression	Hospital Anxiety and Depression Scale (HADS); two subscales (anxiety and depression), each scored 0-21; higher scores indicate greater symptom severity (worse outcome)	Baseline and 12 weeks
Health-related quality of life	EQ-5D-5L; index value ranging from below 0 to 1, where 1 = full health and higher = better; includes a 0-100 visual analogue scale (higher = better health)	Baseline and 12 weeks
Physical activity	International Physical Activity Questionnaire - Short Form; reported as MET-minutes per week; higher values indicate greater physical activity	Baseline and 12 weeks
Lower-limb strength and endurance	30-Second Sit-to-Stand Test; number of full sit-to-stand repetitions completed in 30 seconds; higher counts indicate better lower-limb strength and endurance (better outcome)	Baseline and 12 weeks
Sub-maximal aerobic capacity	2-Minute Step Test; total number of steps completed in 2 minutes; higher counts indicate better aerobic capacity (better outcome).	Baseline and 12 weeks
Muscle strength	Hand grip strength via Jamar handheld dynamometer, recorded in kilograms (best of three attempts per hand); higher values indicate greater muscle strength (better outcome)	Baseline and 12 weeks
Functional mobility	Short Physical Performance Battery (SPPB); composite score 0-12 from balance, 4-metre gait speed, and 5-repetition sit-to-stand; higher scores indicate better lower-extremity function (better outcome)	Baseline and 12 weeks
Orthostatic heart rate response	Heart rate measured supine and on standing (1, 3, 5 min) to screen for orthostatic intolerance	Baseline and 12 weeks
Orthostatic blood pressure response	Blood pressure measured supine and on standing (1, 3, 5 min) to screen for orthostatic hypotension.	Baseline and 12 weeks
Microvascular function	Cutaneous vascular conductance via Laser Speckle Contrast Imaging during local thermal hyperaemia. Expressed as cutaneous vascular conductance (perfusion units/mmHg); higher values indicate greater microvascular reactivity	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Sheffield Hallam University
• Investigators: Principal Investigator: Markos Klonizakis, Sheffield Hallam University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): March 17, 2028

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: physical activity; exercise; rare disease; feasibility study; connective tissue disorder; vEDS; COL3A1
• Additional Relevant MeSH Terms: Dissection, Blood Vessel; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Disease Attributes; Genetic Diseases, Inborn; Hematologic Diseases; Skin Diseases; Congenital Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Aneurysm; Collagen Diseases; Aortic Dissection; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Behavior; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome, Type IV; Rare Diseases; Connective Tissue Diseases; Motor Activity
• Other Study ID Numbers: IRAS361077; 26/NE/0025 (Other Identifier: REC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a small feasibility study not powered for efficacy. Individual participant data will not be shared. Sheffield Hallam University is the Data Controller; data are pseudonymised, stored securely, and retained in line with UK GDPR and institutional policy. Aggregate findings will be disseminated through open-access publication.

Drug and device information, study documents

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