Hamstring Strengthening in Hypermobile Conditions

Effects and Feasibility of Eccentric Hamstring Strengthening in Hypermobility Spectrum Disorders and Hypermobile Ehlers-Danlos Syndrome

The goal of this clinical trial is to determine how strengthening the hamstring muscles affects the knee joint in people living with hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS). The main questions it aims to answer are:

• Does hamstring strengthening reduce the looseness of the knee joint in HSD/hEDS?
• Does hamstring strengthening improve clinical outcomes like pain in people living with HSD/hEDS?

Participants will:

• Attend two exercise classes per week for 12 weeks.
• Visit the laboratory every 4-6 weeks for testing.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypermobile Ehlers-Danlos Syndrome; Hypermobile EDS (hEDS); Hypermobility Type Ehlers-Danlos Syndrome; Hypermobile Spectrum Disorder
• Intervention / Treatment: Behavioral: Progressive resistance exercise with an emphasis on eccentric hamstring loading.

Detailed Description

Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) affect 1 in 500 people, predominantly females. While exercise is known to be beneficial for HSD/hEDS, the effect of eccentric exercise on passive joint stability, the functional capacity to perform daily activities, and quality of life remains unknown. This clinical trial aims to determine the effects of a 12-week eccentric hamstring strengthening intervention for females with HSD/hEDS on knee joint laxity, performance during walking and stair climbing, and quality of life. This study will have important implications for understanding the impacts of exercise in HSD/hEDS. This can then inform clinical guidance and recommendations around lower limb exercise for this population.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ranita Manocha; Phone Number: 4039444224; Email: bettermobilitylab@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • University of Calgary - Foothills Campus
      • Contact: Ranita Manocha; Email: bettermobilitylab@ucalgary.ca
      • Principal Investigator: Ranita Manocha, MD, MSc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Reported diagnosis of HSD or hEDS by a physician
• Meet the 2017 International Diagnostic Criteria for HSD and hEDS
• Clearance to participant in exercise participation, determined using the Get Active Questionnaire

Exclusion Criteria:

• Other acquired or hereditary connective tissue disorder (i.e., rheumatoid arthritis, Marfan syndrome, etc.)
• Currently experiencing daily knee pain
• Prior knee injury or surgery
• Intra-articular knee injection in the last 12 months
• Currently pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Eccentric hamstring exercise; All participants will complete a 12-week supervised lower limb strengthening program focused on eccentric hamstring loading. Participants will complete two training sessions per week with at least 48 hours between training sessions. Multiple classes will be offered each week to increase participation opportunity, with morning classes (8-9am) and evening classes (6-7pm) being offered on Mondays and Thursdays. Each class will be led by the same trained kinesiologist and cover the same training protocol within a given week, regardless of the day or time.

Behavioral: Progressive resistance exercise with an emphasis on eccentric hamstring loading.; The exercise intervention consists of a 12-week supervised lower limb strengthening program focused on eccentric hamstring loading. This program is adapted from a lower limb progressive resistance training protocol that was well-tolerated and effective in people with HSD/hEDS. Each exercise session will start with a 10-minute aerobic warm up. This will be followed by the lower limb strengthening exercises, and a 5-minute aerobic cooldown. The lower limb exercises will include forward lunges and seated machine weights (leg press, leg extension, leg curl, calf raise). At weeks 6-11, eccentric hamstring loading will be initiated by utilizing the 2:1 technique of two limbs performing concentric action at once and then a single limb performing the eccentric action in a seated leg curl machine. This is an established eccentric loading protocol for the hamstring muscle group.; Other Names: Exercise; Progressive Resistance Training; Eccentric Exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Joint Laxity	Anterior knee joint laxity measured in millimeters using a KT-2000 Knee Ligament Arthrometer at 67N, 89N, and 133N of applied force, as well as maximum displacement. Posterior knee joint laxity will be assessed at 67N of applied force. Changes in knee joint laxity at each level of applied force will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Joint Stiffness	Anterior knee joint stiffness calculated from the change in displacement divided by the change in force from 0N to 67N, 67N to 89N, and 89N to 133N. Posterior knee joint stiffness will be calculated between 0N and 67N of force. Changes in stiffness will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Isokinetic eccentric knee flexion strength	Isokinetic eccentric knee flexion strength at 60 degrees per second will be measured using a Biodex Dynamometer. Change in eccentric knee flexion strength will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Isokinetic concentric knee flexion strength	Isokinetic concentric knee flexion strength at 60 degrees per second will be measured using a Biodex dynamometer. Change in concentric knee flexion strength will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Hamstrings:Quadriceps Co-Activation	Co-activation between the hamstrings and quadriceps muscles will be measured using Delsys surface electromyography sensors during dynamometry, the 6-Minute Walk Test, and the stair climb test. Changes in hamstring:quadriceps co-activation will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
6-Minute Walk Test	Functional capacity/performance will be assessed using the 6-Minute Walk Test, which measures the distance in meters that a participant can walk in 6 minutes. Changes in performance will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Pain Severity Score	Pain severity score (from 0 to 40) will be calculated from the pain severity components of the Brief Pain Inventory. The Brief Pain Inventory is a questionnaire that measures the location of pain (body diagram), pain severity (4 questions with numeric rating scales from 0-10, 0 indicating "no pain" and 10 indicating "pain as bad as you can imagine"), medications or treatments, a numeric rating scale (0-100%, 0% indicating "no relief" and 100% indicating "complete relief") for relief of pain from medications or treatments, as well as pain interference (7 questions with numeric rating scales from 0-10, 0 indicating "does not interfere" and 10 indicating "completely interferes"). Changes in pain severity score will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Safety of the Intervention	Safety of the intervention will be monitored and determined by the number of adverse events reported by participants to either the exercise kinesiologist during the exercise sessions, or to the research team during data collection or via email.	Monitored throughout the study from baseline to 24 weeks.
Tolerability of the Intervention	Tolerability of the exercise intervention will be assessed using the following metrics: Number of participants that withdraw from the study (along with reasons for withdrawal), number of exercises classes completed after 12 weeks, and pain severity (100mm visual analog scale) before and after each exercise class.	Monitored throughout the study, from baseline to week 24.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability of the Intervention	Participants will be asked open ended questions via an online survey at 12, 18 and 24 weeks after baseline asking about how acceptable they found the exercise program to be.	Measured at the follow up visits for week 12, 18, and 24.
Adherence and Maintenance of Exercises	Adherence to the exercise program and maintenance of the exercises following completion of the 12 weeks of supervised classes will be assessed using open ended questions via an online survey send to participants at 12, 18, and 24 weeks after baseline.	Measured at follow up visits for week 12, 18, and 24.
Knee Joint Range of Motion	Knee joint range of motion will be measured in degrees both actively and passively using a goniometer. Changes in range of motion will be assessed from baseline, 4, 8 , 12, 18, and 24 weeks.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Isometric knee flexion and extension strength	Isometric knee flexion and extension strength will be measured using dynamometry at 90 degrees of knee flexion. Changes in isometric flexion and extension strength will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Stair Climb Test	Functional capacity/performance will also be assessed using a Stair Climb Test, which measures the time that a participant can ascend and descent a set of stairs. Changes in performance will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Pain Interference Score	Pain interference score (from 0 to 70) will be calculated from the pain severity components of the Brief Pain Inventory. The Brief Pain Inventory is a questionnaire that measures the location of pain (body diagram), pain severity (4 questions with numeric rating scales from 0-10, 0 indicating "no pain" and 10 indicating "pain as bad as you can imagine"), medications or treatments, a numeric rating scale (0-100%, 0% indicating "no relief" and 100% indicating "complete relief") for relief of pain from medications or treatments, as well as pain interference (7 questions with numeric rating scales from 0-10, 0 indicating "does not interfere" and 10 indicating "completely interferes").Changes in pain interference score will be assessed from baseline to 4, 8, 12, 18, and 24 weeks after baseline.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Knee Pain	Knee pain will be determined before and after each exercise session using a 100mm visual analog scale (VAS), with 0 indicating "no pain" and 100 indicating "pain as bad as you can imagine". Knee pain will also be determined at baseline and each follow up assessment using a 100mm VAS for the average knee pain over the last 7 days during rest and during walking, with 0 indicating "no pain" and 100 indicating "pain as bad as you can imagine".	Measured before and after each exercise class, and at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Kinesiophobia	Fear related to physical activity will be measured using the Tampa Scale for Kinesiophobia at baseline and each follow up assessment. The Tampa Scale is scored from 17 questions related to pain, injury, physical activity, and fear. The answers for each question are structured as a 4 point Likert scale (1 - "strongly disagree", 2 - "disagree", 3 - "agree", or 4 - "strongly agree").	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Fatigue	Generalized fatigue will be measured using the Fatigue Severity Scale (FSS) at baseline and each follow up assessment. The FSS contains 9 questions relating to fatigue on a 7 point Likert scale. A 100mm visual analog scale will also accompany the FSS asking to "indicate on the line the point that best describes your fatigue during the past week", with 0 indicating "very alert" and 100 indicating "extremely fatigued". Additionally, a 100mm visual analog scale for fatigue will be measured before and after each exercise class with with 0 indicating "very alert" and 100 indicating "extremely fatigued".	Measured before and after each exercise class, and at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Physical Activity Level	Physical activity levels over the past 7 days will be quantified at baseline and at each follow up assessment using the International Physical Activity Questionnaire (IPAQ). The IPAQ looks at the duration of time spent doing moderate or vigorous activities across job-related physical activity, transportation physical activity, housework/house maintenance/caring for family and recreation/sport/leisure time physical activity.	Measured at all 6 outcome assessments (baseline, 4, 8, 12, 18, and 24 weeks).
Impact of Hypermobility	The impacts of hypermobility on quality of life and physical function will be assessed using the Bristol Impact of Hypermobility (BiOH) questionnaire. The BiOH is scored from 0 to 360, with higher scores indicating greater severity.	Measured at baseline and each follow up assessment at 4, 8, 12, 18, and 24 weeks.
Quality of Life	Quality of life will also be measured using the RAND 36-item short form (SF-36). The SF-36 contains 36 multiple choice questions that are reported as 8 domains, including physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health.	Measured at baseline and each follow up assessment at 4, 8, 12, 18, and 24 weeks.
Knee Injury and Osteoarthritis Outcome Score	The Knee Injury and Osteoarthritis Outcome Score (KOOS) is a questionnaire which measures quality of life and functional outcomes within domains of pain, symptoms, activities of daily living, sport/recreation, and knee-related quality of life. Each domain includes questions with 5-point Likert scales, including how often is your knee painful (never, monthly, weekly, daily, always), symptom severity (none, mild, moderate, severe, extreme), symptom presentations (never, rarely, sometimes, often, always), difficulty with activities (none, mild, moderate, severe, extreme), lifestyle modifications (not at all, mildly, moderately, severely, totally), and concerns (not at all, mildly, moderately, severely, extremely).	Measured at baseline and at each follow up assessment at 4, 8, 12, 18, and 24 weeks.
Knee Joint Proprioception	Knee joint proprioception will be measured with a joint angle reproduction test using isokinetic dynamometer. The participant will be moved to a particular knee angle, then asked to reproduce this knee angle. The error in degrees between the original joint angle and the participant's reproduced joint angle will be calculated.	Measured at baseline and at each follow up assessment at 4, 8, 12, 18, and 24 weeks.
Work Status	Work Status will be reported at baseline and each follow up assessment as a multiple choice question with the following answers: not working by choice, part-time student, full-time student, retired, working full-time, working part-time, on temporary medical leave or short-term disability, on long-term disability (private, Canada Pension Plan Disability, or Workers' Compensation Board-Alberta income supplementation), other (please specify).	Measured at baseline and each follow up assessment at 4, 8, 12, 18 and 24 weeks.

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Ranita Manocha, University of Calgary

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; Knee; Female; strengthening; Ehlers-Danlos Syndrome; Hypermobility; eccentric; Hypermobile Ehlers-Danlos Syndrome; Joint Laxity; Joint Stiffness; Hypermobility Spectrum Disorders
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases; Joint Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Hematologic Diseases; Skin Diseases; Congenital Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Collagen Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Behavior; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Ehlers-Danlos Syndrome; Joint Instability; Motor Activity; Ehlers-Danlos syndrome type 3; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: REB26-0442

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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