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Enrolling by invitationNCT07657507Updated Oct 22, 2026

Presentation of Young Adults With and Without Joint Hypermobility

An observational study in Hypermobile Ehlers-Danlos Syndrome and Postural Orthostatic Tachycardia Syndrome (POTS), sponsored by Clarkson University. Enrolling by invitation at 1 site in United States. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-22.

Sponsored by Clarkson University · Observational

Updated Oct 22, 2026Now Enrolling by invitationStart date movedGo to Updates ↓
Study type
Observational
Model
Case-control
Time perspective
Prospective
Enrollment
100
Ages
18 Years to 60 Years
Sex
All
01

Study summary

People with multiple hypermobile joints are diagnosed with Generalized Joint Hypermobility (GJH) when asymptomatic, or Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorder (HSD) when symptomatic (hEDS/HSD, or 'HSD' here). GJH likely affects about 20% of the U.S. population, while HSD affects 0.5-3% of the US population. Although joint hypermobility is the most visible presentation of HSD, it is a systemic connective tissue disorder affecting multiple body systems. Due to frequent health concerns, HSD may contribute to more than 30% of patients in chronic pain, rheumatology, orthopedic and physical therapy clinics. It is still unclear why some people have asymptomatic hypermobility and others develop complex chronic health issues. However, recent research suggests that the transition might be triggered by severe physiological stress, such as viral infection.

HSD is commonly associated with Postural Orthostatic Tachycardia Syndrome (POTS) and Mast Cell Activation Syndrome (MCAS), as well as gastrointestinal (GI) problems. Recent research suggests that persistent inflammation due to MCAS or COVID may trigger HSD symptoms. The correlation between POTS and HSD may be due to effects of HSD on the autonomic nervous system or to inflammation triggering both conditions. It is also unclear whether body awareness and coordination deficits seen in symptomatic HSD are due to the fundamental connective tissue disorder or due to pain and injuries in HSD. This study seeks to determine whether asymptomatic hypermobile individuals (GJH) also have balance and coordination deficits. The current study hopes to identify factors that correlate with a transition from asymptomatic GJH to symptomatic HSD by following a group of Health Science students forward in time. The study will collect baseline health information including relevant diagnoses, symptoms and function. Physical measurements will include standard clinical tests performed by physical therapists: joint hypermobility and instability, standing balance, neck movement control, and heart rate in response to standing from lying down. The study is likely to last for at least 10 years to follow participants over time.

Read the detailed description

Most hyper mobility-related research is conducted by clinical researchers, who are generally limited to recruiting research subjects from patients who present to their clinics. There are few opportunities for longitudinal studies of asymptomatic or 'healthy' individuals to identify potential triggers prospectively and to compare to people who do not develop symptoms. A health care academic institution provides the ideal environment for a prospective study, somewhat like the 'Nurses Health Study'* that followed a population of nurses throughout their lives.

The study will collect initial data on:

  • Current diagnoses related to HSD, MCAS, and POTS (questionnaire)
  • Current symptoms associated with HSD, MCAS and POTS (questionnaire)
  • Overall quality of life (questionnaire)
  • Physical measures for diagnosing joint hypermobility and instability
  • Physical screening for POTS
  • Physical screening for body awareness, balance and coordination

Objectives and Hypotheses

  1. What is the prevalence of HSD, POTS and MCAS in a 'healthy' young adult population?
  2. How often are HSD, POTS and MCAS undiagnosed in a 'healthy' young adult population?
  3. Are there factors that trigger or precede the development of widespread symptoms in people who have GJH, causing them to develop HSD?
  4. What risk factors are associated with increased likelihood that an individual will develop POTS, MCAS, or HSD?
  5. Do balance or motor control in the neck differ in asymptomatic joint hypermobility compared to symptomatic hypermobility?
  6. If coordination impairments exist in asymptomatic people with hypermobility, does that predict development of HSD?

Questionnaires will be on secure Google Forms accessed through participants' phones or other electronic devices. Participants may pause and return to the questionnaires if they choose. We intend for the questionnaires to require no more than 30 minutes to complete; we may need to eliminate questions from the current list to achieve this.

Physical measurements will be performed only at the initial data collection. These measurements will be performed by licensed physical therapists, who may be assisted by physical therapy graduate students with adequate training to assist in selected data collection. Data collection will take place in Clarkson Hall. Measurements are likely to be performed at 'stations' by various assessors, but any participant who would like to be in a private room for any or all of the assessment may request that. Physical measurements are likely to take about 30 minutes.

Each year, we will follow up by emailing participants asking them to complete questionnaires that will be a subset of the initial set of questions. Questionnaires will again be implemented through secure Google Forms.

02

Conditions studied

  • Hypermobile Ehlers-Danlos Syndrome
  • Postural Orthostatic Tachycardia Syndrome (POTS)

Keywords

  • hypermobile Ehlers-Danlos Syndrome
  • Hypermobility Spectrum Disorders
  • Risk factors
03

In context

Ehlers-Danlos syndrome type 3

28 studies on the registry are indexed under Ehlers-Danlos syndrome type 3; 9 are open to participants now.

This study's planned enrollment of 100 is above the median of 39 across 12 observational studies indexed under Ehlers-Danlos syndrome type 3.

Browse Ehlers-Danlos syndrome type 3 studies →

Lead sponsor

Clarkson University is the lead sponsor of 7 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Health Science graduate students are typically 20-35 years old, though some non-traditional students might be slightly older.

Eligibility criteria

Inclusion Criteria: Clarkson University Health Sciences students. -

Exclusion Criteria: Other physical conditions that preclude collecting >25% of physical measurements at initial data collection.

-

05

Study design

Observational model
Case-control
Time perspective
Prospective
Enrollment
100 participants (estimated)
Target follow-up
5 Years
Patient registry
Yes

Groups and cohorts

  • hypermobile - symptomatic

    People who meet the diagnostic criteria for hEDS or HSD

  • non-hypermobile

    People who do not meet the diagnostic criteria for generalized joint laxity, hEDS or HSD

  • hypermobile - non-symptomatic

    People with generalized joint laxity but not meeting diagnostic criteria for hEDS/HSD

06

What researchers measure

Primary outcomes

  1. Hypermobility status

    Subject meets diagnostic criteria for generalized joint hypermobility, hypermobile Ehlers-Danlos Syndrome or Hypermobility Spectrum Disorders. This will be nominal: None, GJH, HSD hEDS.

    Time frame: 5 years

Secondary outcomes

  1. EuroQol, 5-Dimension, 5-Level (EQ-5D-5L)

    5-domain quality of life measure: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. It scores each domain on a 1-5 scale, where higher scores indicate greater disability. The scores are not summed.

    Time frame: 5 years

  2. Hypermobility Spider Questionnaire

    31-item questionnaire quantifying symptoms in 8 domains: Neuromusculoskeletal, Pain, Fatigue, Gastrointestinal, Cardiac Dysautonomia, Urogenital, Anxiety, Depression. Each domain is scored 0-100, where 0 is no symptoms in that domain, and 100 is the most symptoms in that domain.

    Time frame: 5 years

Other outcomes

  1. Physical activity

    Modified International Physical Activity Questionnaire short form measures vigorous, moderate, and light exercises and computes 'metabolic minutes' or METs. Minimum score of 0 indicates no exercise. The maximum possible score allowed is 19,278.

    Time frame: 5 years

  2. New comorbidities

    New presentation of POTS or MCAS

    Time frame: 5 years

07

Study locations

1 site
  • Clarkson University, Lewis School of Health & Life Sciences
    Potsdam, New York 13699, United States
08

References and documents

Publications

  • Weinstock LB, Brook JB, Walters AS, Goris A, Afrin LB, Molderings GJ. Mast cell activation symptoms are prevalent in Long-COVID. Int J Infect Dis. 2021 Nov;112:217-226. doi: 10.1016/j.ijid.2021.09.043. Epub 2021 Sep 23. PubMed 34563706 ↗
  • Wang E, Ganti T, Vaou E, Hohler A. The relationship between mast cell activation syndrome, postural tachycardia syndrome, and Ehlers-Danlos syndrome. Allergy Asthma Proc. 2021 May 1;42(3):243-246. doi: 10.2500/aap.2021.42.210022. PubMed 33980338 ↗
  • Tinkle B, Castori M, Berglund B, Cohen H, Grahame R, Kazkaz H, Levy H. Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):48-69. doi: 10.1002/ajmg.c.31538. Epub 2017 Feb 1. PubMed 28145611 ↗
  • Simmonds JV. Masterclass: Hypermobility and hypermobility related disorders. Musculoskelet Sci Pract. 2022 Feb;57:102465. doi: 10.1016/j.msksp.2021.102465. Epub 2021 Oct 13. PubMed 34808594 ↗
  • Russek LN, Stott P, Simmonds J. Recognizing and Effectively Managing Hypermobility-Related Conditions. Phys Ther. 2019 Sep 1;99(9):1189-1200. doi: 10.1093/ptj/pzz078. PubMed 31158283 ↗
  • Abed H, Ball PA, Wang LX. Diagnosis and management of postural orthostatic tachycardia syndrome: A brief review. J Geriatr Cardiol. 2012 Mar;9(1):61-7. doi: 10.3724/SP.J.1263.2012.00061. PubMed 22783324 ↗
  • Puyol A, King M, Ganderton C, Hu S, Tirosh O. Balance Assessments Using Smartphone Sensor Systems and a Clinician-Led Modified BESS Test in Soccer Athletes with Hip-Related Pain: An Exploratory Cross-Sectional Study. Sensors (Basel). 2026 Feb 6;26(3):1061. doi: 10.3390/s26031061. PubMed 41682576 ↗
  • Ormiston CK, Swiatkiewicz I, Taub PR. Postural orthostatic tachycardia syndrome as a sequela of COVID-19. Heart Rhythm. 2022 Nov;19(11):1880-1889. doi: 10.1016/j.hrthm.2022.07.014. Epub 2022 Jul 16. PubMed 35853576 ↗
  • Griggs M, Daylor V, Petrucci T, Weintraub A, Huff M, Willey S, Byerly K, Loizzi B, Morningstar J, Ball LE, Bethard JR, Drake R, Sharma A, Eichinger JK, Nichols M, Kautz S, Shapiro S, Maitland A, Patel S, Norris RA, Gensemer C. Proteomic discoveries in hypermobile Ehlers-Danlos syndrome reveal insights into disease pathophysiology. Immunohorizons. 2025 Sep 17;9(10):vlaf044. doi: 10.1093/immhor/vlaf044. PubMed 40972649 ↗
  • Ganesh R, Munipalli B. Long COVID and hypermobility spectrum disorders have shared pathophysiology. Front Neurol. 2024 Sep 5;15:1455498. doi: 10.3389/fneur.2024.1455498. eCollection 2024. PubMed 39301475 ↗
  • Ewer ER, De Pauw R, Kazkazk H, Ninis N, Rowe P, Simmonds JV, De Wandele I. The Spider: a visual, multisystemic symptom impact questionnaire for people with hypermobility-related disorders-validation in adults. Clin Rheumatol. 2024 Sep;43(9):3005-3017. doi: 10.1007/s10067-024-07071-7. Epub 2024 Jul 31. PubMed 39085705 ↗
  • Ernst MJ, Williams L, Werner IM, Crawford RJ, Treleaven J. Clinical assessment of cervical movement sense in those with neck pain compared to asymptomatic individuals. Musculoskelet Sci Pract. 2019 Oct;43:64-69. doi: 10.1016/j.msksp.2019.06.006. Epub 2019 Jul 2. PubMed 31277033 ↗
  • Collins Hutchinson ML, Liang E, Fuster E, Blitshteyn S. Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome. Auton Neurosci. 2025 Dec;262:103356. doi: 10.1016/j.autneu.2025.103356. Epub 2025 Oct 14. PubMed 41118678 ↗
  • Cleland C, Ferguson S, Ellis G, Hunter RF. Validity of the International Physical Activity Questionnaire (IPAQ) for assessing moderate-to-vigorous physical activity and sedentary behaviour of older adults in the United Kingdom. BMC Med Res Methodol. 2018 Dec 22;18(1):176. doi: 10.1186/s12874-018-0642-3. PubMed 30577770 ↗
  • Molderings GJ, Brettner S, Homann J, Afrin LB. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. J Hematol Oncol. 2011 Mar 22;4:10. doi: 10.1186/1756-8722-4-10. PubMed 21418662 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No — To ensure privacy of health information in a fairly small subject pool.

09

Updates

1 registry update since Sep 25, 2026
Status
Not yet recruiting→Enrolling by invitation
changed Oct 22, 2026
Start date
Jun 20, 2026→Sep 23, 2026 (actual)
Oct 22, 2026
Contact
No study contact listed any more: removed L•••@clarkson.edu · •••2851; removed s•••@clarkson.edu · •••7622
Oct 22, 2026
Site contacts
Changed at 1 site. See the sites
Show the site
  • Clarkson University, Lewis School of Health & Life Sciences · Potsdam, United StatesContact removed s•••@clarkson.edu · •••7622Contact removed h•••@clarkson.edu · •••3786Contact removed (no phone or email listed)
Oct 22, 2026
Show all 1 update
  1. Oct 22, 2026
    Not yet recruiting→Enrolling by invitation
    Start date Jun 20, 2026→Sep 23, 2026 (now actual)
    Contact No study contact listed any more: removed L•••@clarkson.edu · •••2851; removed s•••@clarkson.edu · •••7622
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Clarkson University, Lewis School of Health & Life Sciences · Potsdam, United StatesContact removed s•••@clarkson.edu · •••7622Contact removed h•••@clarkson.edu · •••3786Contact removed (no phone or email listed)
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07657507
Lead sponsor
Clarkson University
Responsible party
Leslie Russek (Professor Emerita, Clarkson University) — Principal investigator
First posted
Jun 18, 2026
Start date
Sep 23, 2026
Primary completion
Jun 20, 2036 (estimated)
Completion
Jun 20, 2036 (estimated)
Last update
Oct 22, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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