Vascular Ehlers Danlos Syndrome

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.

This research study will investigate whether people with vascular Ehlers-Danlos syndrome (vEDS), a rare inherited condition, have problems with the way their body stores and uses fat (adipose tissue). vEDS is caused by changes in a gene called COL3A1, which makes a protein important for the structure of many tissues. While vEDS is best known for making blood vessels fragile, there is some early evidence that it may also affect fat tissue and increase the risk of problems such as insulin resistance (where the body does not respond properly to insulin) and diabetes. Fat tissue is important for keeping the body healthy. It stores extra energy, but it also sends signals to other organs. If fat tissue cannot expand or work properly, fat can build up in the liver or muscles instead, leading to high blood sugar, high cholesterol, and greater risk of diabetes and heart disease. In this study, we will invite 12-17 adults with genetically confirmed vEDS to take part, along with a group of age-, sex-, and weight-matched controls without vEDS. Participants will attend a research visit at Addenbrooke's Hospital, Cambridge. They will have measurements of body fat distribution (using a DEXA scan), a liver scan, blood tests, and a standard oral glucose tolerance test (drinking a sugary drink with blood samples before and after). Some participants may also choose to provide a small fat biopsy under local anaesthetic to allow more detailed analysis of tissue structure. The main aim is to see whether people with vEDS show changes in fat distribution and insulin sensitivity compared to those without vEDS.

This is a prospective, Phase 3, randomized, double-blind, placebo-controlled efficacy study to evaluate celiprolol in patients genetically confirmed as COL3A1-positive vEDS using a decentralized clinical trial design.

Vascular Ehlers-Danlos Syndrome (VEDS) is caused by pathogenic variants of the COL3A1 gene, resulting abnormal Type III collagen protein. This impacts the body's connective tissue and makes people with VEDS at high risk of spontaneous aortic and arterial rupture, pneumothorax, and hollow organ perforation across the age spectrum. Given this risk and high potential for lethality, VEDS is considered the most severe type of Ehlers-Danlos Syndrome. In addition, many patients experience chronic pain and fatigue, sleep disturbances, and mental health challenges. As is the case for many patients with chronic illness, stress, anxiety, and depression are often present over the course of the disease. Despite the antecedent, stress and anxiety trigger a sympathetic nervous system (SNS) response in the body, which, over a period of time, can have detrimental effects both physiologically and psychologically for patients. Recent studies have begun to use biofeedback techniques to teach patients non-pharmacological strategies for managing their autonomic nervous system. One such program, Heartmath®, has been successful in helping patients lower stress, anxiety, and systolic blood pressure. This pilot trial was established to assess the effectiveness of a virtually based heart coherence program in a population with a chronic aortopathy in an effort to establish a larger, multi-provider program that also encompasses other cardiovascular populations.