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

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.

• Co-designed exercise-based lifestyle intervention (Behavioral): 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.

Primary outcomes

• Recruitment rate [From study start through completion of recruitment, up to 12 months]: Proportion of eligible participants who consent to take part, expressed as a monthly recruitment rate.
• Retention rate [12 weeks]: Proportion of randomised participants completing the 12-week intervention (progression target ≥80%)
• Adherence [Over the 12-week intervention period]: 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
• Data completeness [Baseline and 12 weeks]: Proportion of participants completing outcome measures at baseline and 12 weeks (target ≥75%)
• Acceptability [12 weeks]: Acceptability assessed via a questionnaire informed by the Theoretical Framework of Acceptability (seven constructs, 5-point Likert scale), supplemented by post-intervention interviews
• Adverse events and serious adverse events [Throughout the 12-week intervention period]: Number, type and severity of adverse events and serious adverse events, reviewed by the independent Data Safety Committee.

Secondary outcomes

• Fatigue [Baseline and 12 weeks]: FACIT-Fatigue Scale (Functional Assessment of Chronic Illness Therapy - Fatigue); score range 0-52; higher scores indicate less fatigue (better outcome)
• Anxiety and depression [Baseline and 12 weeks]: Hospital Anxiety and Depression Scale (HADS); two subscales (anxiety and depression), each scored 0-21; higher scores indicate greater symptom severity (worse outcome)
• Health-related quality of life [Baseline and 12 weeks]: 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)
• Physical activity [Baseline and 12 weeks]: International Physical Activity Questionnaire - Short Form; reported as MET-minutes per week; higher values indicate greater physical activity
• Lower-limb strength and endurance [Baseline and 12 weeks]: 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)
• Sub-maximal aerobic capacity [Baseline and 12 weeks]: 2-Minute Step Test; total number of steps completed in 2 minutes; higher counts indicate better aerobic capacity (better outcome).
• Muscle strength [Baseline and 12 weeks]: Hand grip strength via Jamar handheld dynamometer, recorded in kilograms (best of three attempts per hand); higher values indicate greater muscle strength (better outcome)
• Functional mobility [Baseline and 12 weeks]: 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)
• Orthostatic heart rate response [Baseline and 12 weeks]: Heart rate measured supine and on standing (1, 3, 5 min) to screen for orthostatic intolerance
• Orthostatic blood pressure response [Baseline and 12 weeks]: Blood pressure measured supine and on standing (1, 3, 5 min) to screen for orthostatic hypotension.
• Microvascular function [Baseline and 12 weeks]: 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

Sex: All, ages: 18 Years to any

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

• Markos Klonizakis, Principal investigator, Sheffield Hallam University