On the 25th March, Prof Manoj Sivan and colleagues published the results of their research project, ‘Developing and Testing a Personalised Dysautonomia Management Protocol (DMP) in ME/CFS and Long Covid – A Proof-Of-Concept Study', which was funded by the ME Association's Ramsay Research Fund.
Dr Katrina Pears, Research Coordinator for the MEA has conducted an video interview with Prof Manoj Sivan, which you can watch below, alongside a summary of the research and results.
Testing a Personalised Dysautonomia Management Protocol in Patients with Orthostatic Intolerance and a Diagnosis of ME/CFS or Long Covid
By Julia Barr, Lowri Marsden, Theshan Dassanayake, Norah Almutairi, Vikki McKeever, Tarek Gaber, Rachel Tarrant, Belinda Godfrey, Sharon Witton, and Manoj Sivan[1][2][3][4].
This is a summary report produced initially by Adobe AI on 15 April 2026 and edited for accuracy and grammar by The ME Association. It provides an overview of the feasibility study for a personalised conservative management protocol of autonomic dysfunction in patients with ME/CFS and Long Covid experiencing orthostatic intolerance.
Feasibility of Dysautonomia Management Protocol
A pilot study assessed an 8-week personalised, supervised intervention for patients with ME/CFS and Long Covid exhibiting orthostatic intolerance, showing modest improvements in autonomic symptoms and heart rate.
Participant Recruitment and Baseline Characteristics
The study screened 183 patients, with 32 eligible and 22 consenting; 16 completed the program.
- 183 screened; 151 non-diagnostic results
- 32 eligible; 22 consented; 16 completed
- Mean age 39 years; range 17.25–63.2
- 90.9% female; predominantly White British
- 63.6% had ME/CFS; 36.4% had Long Covid
- Average dysautonomia duration 7 years
- 90.9% met Postural Orthostatic Tachycardia Syndrome (PoTS) criteria at baseline; 2 had Orthostatic Hypotension (OH)
- Common comorbidities: fibromyalgia (n=10), asthma (n=7), EDS/hypermobility (n=6)
- Most patients on multiple medications; pain relief most common.
Interventions and Program Structure
The 8-week Dysautonomia Management Protocol (DMP) included four sequential, cumulative interventions: fluid and salt intake increases, pacing, and calf activation, with weekly remote follow-up.
- Increase fluid intake to 3 L/day over 2 weeks
- Increase salt intake to 10 g/day over 2 weeks
- Pacing activities to avoid crashes over 2 weeks
- Calf activation movements 10 reps, 3 times daily over 2 weeks
- Weekly Teams meetings for guidance, monitoring, and support
- Tailored to individual needs; monitored via questionnaires and orthostatic testing.
Key Findings
Symptom and autonomic changes
- COMPASS‑31 scores improved by 7.74 points (p=0.045)
- Heart‑rate rise during the Lean Test reduced by 4.8 bpm (p=0.032)
- No significant changes in blood pressure or YRS symptom scores
Autonomic variability
- Many participants fluctuated between PoTS, OH, and borderline profiles
- This suggests that single tests may miss important day‑to‑day variation
Adherence
- No participant completed all four components fully
- Calf activation was easiest; salt intake was hardest
- Weekly reviews may have helped through reassurance and engagement
Safety
- No serious adverse events
- One withdrawal due to an unrelated severe crash
Interpretation
Lifestyle‑based interventions may offer small but measurable improvements in autonomic symptoms and postural heart rate. However, the clinical impact was modest, and the programme was challenging for many to follow consistently. Autonomic symptoms fluctuated widely, highlighting the need for repeated testing and personalised management.
Challenges in Implementing Lifestyle Strategies
Adherence to interventions varied, and the complexity of conditions makes sustained implementation difficult, even with supervised support.
- Calf activation movements most achievable; followed by fluid intake and pacing.
- Salt intake was least well implemented.
- No clear link between adherence levels and symptom improvement due to small sample size.
- Structured weekly reviews may have contributed to perceived benefits through validation and engagement.
- Intervention burden and fatigue may limit patient compliance.
- Longer, less frequent follow-up might improve adherence and detectability of changes.
Safety, Tolerance, and Feasibility of Interventions
Interventions were generally safe and well tolerated, supporting their feasibility in clinical practice.
- No serious adverse events linked to the program.
- Quantitative improvements were modest.
- Interventions are difficult to fully implement within an 8-week period.
- Management should focus on symptom relief and realistic, personalized targets.
- Physiological monitoring should complement, not replace, symptom-based management.
- Longer-term studies are needed to assess full therapeutic potential.
Study Limitations and Future Directions
Small sample size, lack of control group, and reliance on self-report limit the strength of conclusions.
- Over 90% female participants, reflecting epidemiology but limiting generalizability.
- Recruitment challenges due to symptom severity and commitment required.
- Variability in remote testing may introduce measurement errors.
- Statistical significance may be affected by multiple testing; larger, powered studies needed.
- Future research should include control groups, longer durations, pharmacological options, and qualitative assessments.
- Larger studies could clarify whether PoTS and OH are points on a continuum or separate conditions.
Conclusions and Clinical Implications
The study demonstrates modest benefits of a non-pharmacological management protocol, emphasizing realistic expectations and the need for larger, controlled trials.
- The DMP (non‑pharmacological management programme) was safe and doable.
- It led to modest improvements in some symptoms and aspects of autonomic function.
- Some people showed better COMPASS‑31 scores and lower increases in heart rate when standing.
- There were no major changes in blood pressure or overall symptom scores (YRS).
- The improvements were statistically significant, but small in day‑to‑day impact.
- People varied in how much they could follow the programme, and in how much benefit they felt.
- Autonomic symptoms can fluctuate a lot, meaning a single test may not show the full picture.
- The programme can be challenging to stick to, so setting realistic goals is important.
- A personalised, long‑term approach may help people get the most from these strategies.
- More and larger studies are needed to confirm the benefits and refine the programme.
[1] Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS7 4SA, UK
[2] Email: m.sivan@leeds.ac.uk
[3] Leeds Community Healthcare, Leeds LS11 0DL, UK
[4] Department of Rehabilitation Medicine, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA, UK
More Information
- ME Association: Professor Manoj Sivan to develop new protocol for dysautonomia in ME/CFS and Long Covid
- Research: Developing and Testing a Personalised Dysautonomia Management Protocol (DMP) in ME/CFS and Long Covid
