A Phase 1/2 interventional study of Dextrose 20% Prolotherapy and Autologous Platelet-Rich Plasma in Ehlers-Danlos Syndrome Hypermobility Type (hEDS), Ehlers-Danlos Syndrome (EDS) and Joint Hypermobility, sponsored by Manhattan Pain Medicine, PLLC. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-06.
Sponsored by Manhattan Pain Medicine, PLLC · Phase 1/2, Interventional, and Treatment
This clinical trial is designed to evaluate whether a stepwise injection-based treatment approach can reduce pain and improve function in adults with joint hypermobility, connective tissue laxity, and joint instability.
Joint hypermobility occurs when joints move beyond their normal range, often because of looser connective tissue. For some patients, this can contribute to chronic pain, recurrent instability, reduced function, and disability. This study focuses on adults with hypermobile Ehlers-Danlos syndrome (hEDS), hypermobility spectrum disorder (HSD), or joint instability after injury who have already completed physical therapy without adequate relief.
The main question this study aims to answer is whether the first treatment step, dextrose prolotherapy, can reduce pain by 40% or more two weeks after the second injection.
Participants will receive treatment in a step-by-step sequence, based on their response:
Step 1: Dextrose prolotherapy A dextrose-based injection used to stimulate a healing response in ligament, tendon, or joint-supporting tissue.
Step 2: Platelet-rich plasma (PRP) An injection prepared from the participant's own blood, designed to support tissue repair and recovery.
Step 3: Doxycycline injections A low-dose injectable treatment used in this study to help protect joint-supporting tissue. It is not being used to treat infection.
Alternative option: Hyaluronic acid injections An injection into the joint that may be offered if the earlier treatment steps do not provide enough improvement.
Each treatment step begins with two injections, given approximately two weeks apart. If a participant improves by 40% or more, they may continue with that treatment pathway. If they do not improve enough, they may be offered the next step in the study.
Participants will be followed for up to 12 months, with study visits used to monitor pain, function, treatment response, and safety.
This is a prospective, open-label, single-arm, step-care interventional study evaluating a structured regenerative medicine treatment protocol for adults with symptomatic joint hypermobility or instability who have failed conservative therapy including physical therapy.
All eligible participants begin with dextrose prolotherapy (20% final concentration). Response is assessed at 2 weeks after the second injection using the Global Percentage of Improvement (GPI) scale. Participants who improve by 40% or more continue with that treatment. Those who do not improve enough are offered the next treatment in the sequence.
The step-care sequence is:
Phase 1: Dextrose prolotherapy (20% dextrose with local anesthetic) Phase 2: Autologous platelet-rich plasma (PRP) prolotherapy Phase 3: Investigational injectable doxycycline hyclate prolotherapy (10 mg/mL; 5-25 mg per joint site; maximum 100 mg per session) Alternative pathway: Visco-3 hyaluronic acid viscosupplementation (FDA-approved for knee osteoarthritis; off-label use in other joints disclosed in consent)
Each phase follows the same cycle: 2 injections approximately 2 weeks apart, followed by a decision point at 2 weeks after the second injection. The dextrose phase decision point is the study primary endpoint.
Outcome measures collected include the Brief Pain Inventory (BPI), Global Percentage of Improvement (GPI), and region-appropriate joint-specific functional measures (DASH for upper extremity, KOOS for knee, LEFS for lower extremity, ODI for spine). Long-term follow-up occurs at 3, 6, and 12 months.
Safety is monitored continuously. An Independent Medical Monitor reviews all serious adverse events. The injectable doxycycline use is investigational; an IND exemption determination request has been submitted to the FDA. Enrollment into the doxycycline phase will not begin until the FDA determination is received and IRB approval is in place.
The study is investigator-initiated with no external funding. It is conducted at a single site - Manhattan Pain Medicine, New York, NY.
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 32 across 16 interventional studies indexed under Ehlers-Danlos syndrome type 3.
Browse Ehlers-Danlos syndrome type 3 studies →This is the only study on the registry with Manhattan Pain Medicine, PLLC as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Symptomatic joint hypermobility or instability attributable to one of the following:
Objective evidence of instability or hypermobility at one or more target joints, defined as at least one of:
Additional eligibility for the Hyaluronic Acid (HA) alternative pathway - a participant may enter the HA pathway if ALL of the following apply, in addition to the inclusion criteria above:
Has completed at least one regenerative medicine phase (dextrose, PRP, or doxycycline) and either
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All participants receive a step-care sequence beginning with dextrose prolotherapy. Those who do not improve by 40% or more are offered rotation to platelet-rich plasma (PRP) prolotherapy, then to investigational doxycycline prolotherapy. A hyaluronic acid viscosupplementation pathway is available as an alternative for participants who do not respond to or cannot tolerate the regenerative steps.
Drug: Dextrose 20% Prolotherapy · Biological: Autologous Platelet-Rich Plasma · Drug: Doxycycline Hyclate Injectable (Investigational) · Device: Visco-3 Sodium Hyaluronate Viscosupplementation
Hypertonic dextrose solution injected at periarticular ligament-bone junctions at 20% final concentration, combined with local anesthetic. Two injections approximately 2 weeks apart per phase. Up to 4 injections total.
Leukocyte-poor platelet-rich plasma prepared from a 30-60 mL autologous whole blood draw using an FDA-cleared PRP preparation system. Two injections approximately 2 weeks apart per phase. Up to 4 injections total.
Also known as: PRP
Doxycycline hyclate 10 mg/mL reconstituted from commercially available lyophilized powder at point of care, combined with 20% dextrose and local anesthetic. Dose: 5-25 mg per joint site; maximum 100 mg per session. Two injections approximately 2 weeks apart per phase. Up to 4 injections total. Use as prolotherapy agent is investigational.
Visco-3 (sodium hyaluronate 25 mg/2.5 mL), FDA-approved for knee osteoarthritis. Used as an alternative pathway for participants who do not respond to or cannot tolerate regenerative phases. Up to 3 syringes per joint per course. Off-label use in non-knee joints is disclosed in the informed consent form.
Global Percentage of Improvement (GPI) Responder Rate After Dextrose Prolotherapy
Proportion of participants achieving at least 40% improvement on the Global Percentage of Improvement (GPI) scale relative to baseline. The GPI is a validated patient-reported outcome measure used in prolotherapy research in which participants rate their overall percentage of improvement from 0% (no improvement) to 100% (complete improvement). A participant is classified as a responder if they report 40% or greater improvement. This threshold also serves as the step-care decision rule: responders continue dextrose; non-responders are offered rotation to the next treatment.
Time frame: 2 weeks after the second dextrose prolotherapy injection (approximately 4 weeks after enrollment)
Change in Brief Pain Inventory (BPI) Pain Severity Score
Change from baseline in the Brief Pain Inventory (BPI) pain severity subscale, a validated 4-item patient-reported measure assessing worst, least, average, and current pain on a 0-10 numeric rating scale. Scores range from 0 to 10, where 0 indicates no pain and 10 indicates pain as bad as you can imagine. Higher scores indicate worse outcome.
Time frame: Baseline, 2 weeks after second injection of each phase, and at 3, 6, and 12 months
Change in Brief Pain Inventory (BPI) Pain Interference Score
Change from baseline in the Brief Pain Inventory (BPI) interference subscale, a validated 7-item patient-reported measure assessing how pain interferes with general activity, mood, walking, work, relationships, sleep, and enjoyment of life on a 0-10 numeric rating scale. Scores range from 0 to 10 per item and are averaged to a total interference score of 0 to 10, where 0 indicates no interference and 10 indicates complete interference. Higher scores indicate worse outcome.
Time frame: Baseline, 2 weeks after second injection of each phase, and at 3, 6, and 12 months
Change in Disabilities of the Arm, Shoulder and Hand (DASH) Score
Change from baseline in the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, a validated 30-item patient-reported outcome measure assessing physical function and symptoms in people with musculoskeletal disorders of the upper extremity. Scores range from 0 to 100, where 0 indicates no disability and 100 indicates maximum disability. Higher scores indicate worse outcome. Administered to participants whose primary target joint is in the upper extremity.
Time frame: Baseline, 2 weeks after second injection of each phase, and at 3, 6, and 12 months
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS)
Change from baseline in the Knee Injury and Osteoarthritis Outcome Score (KOOS), a validated patient-reported outcome measure assessing symptoms, pain, function in daily living, function in sport and recreation, and knee-related quality of life. Each of five subscales is scored from 0 to 100, where 0 indicates extreme problems and 100 indicates no problems. Higher scores indicate better outcome. Administered to participants whose primary target joint is the knee.
Time frame: Baseline, 2 weeks after second injection of each phase, and at 3, 6, and 12 months
Change in Lower Extremity Functional Scale (LEFS) Score
Change from baseline in the Lower Extremity Functional Scale (LEFS), a validated 20-item patient-reported outcome measure assessing function in people with lower extremity musculoskeletal conditions. Scores range from 0 to 80, where 0 indicates inability to perform any activities and 80 indicates no difficulty with any activities. Higher scores indicate better outcome. Administered to participants whose primary target joint is in the lower extremity (excluding knee).
Time frame: Baseline, 2 weeks after second injection of each phase, and at 3, 6, and 12 months
Change in Oswestry Disability Index (ODI) Score
Change from baseline in the Oswestry Disability Index (ODI), a validated 10-item patient-reported outcome measure assessing degree of disability and quality of life in people with low back pain. Scores range from 0 to 100, where 0 indicates no disability and 100 indicates maximum disability. Higher scores indicate worse outcome. Administered to participants whose primary target joint is in the spine.
Time frame: Baseline, 2 weeks after second injection of each phase, and at 3, 6, and 12 months
Global Percentage of Improvement (GPI) Responder Rate After PRP Prolotherapy
Proportion of participants rotated to platelet-rich plasma (PRP) prolotherapy who achieve at least 40% improvement on the GPI scale at the PRP phase decision point, among participants who did not respond to dextrose prolotherapy.
Time frame: 2 weeks after the second PRP prolotherapy injection
Global Percentage of Improvement (GPI) Responder Rate After Doxycycline Prolotherapy
Proportion of participants rotated to investigational doxycycline prolotherapy who achieve at least 40% improvement on the GPI scale at the doxycycline phase decision point, among participants who did not respond to dextrose and PRP prolotherapy.
Time frame: 2 weeks after the second doxycycline prolotherapy injection
Global Percentage of Improvement (GPI) Response After Hyaluronic Acid Viscosupplementation
GPI score at end-of-course assessment among participants who entered the alternative hyaluronic acid (HA) viscosupplementation pathway after failure of or adverse reaction to regenerative phases. Reported descriptively; not compared to regenerative phase outcomes.
Time frame: 2 weeks after the final hyaluronic acid injection of the course
Durability of Response: Global Percentage of Improvement (GPI) Score at 3, 6, and 12 Months
Global Percentage of Improvement (GPI) score at 3, 6, and 12 months from the primary endpoint assessment, evaluating maintenance of treatment response and need for additional treatment over time. The GPI is a patient-reported scale ranging from 0% to 100%, where 0% indicates no improvement and 100% indicates complete improvement relative to baseline. Higher scores indicate better outcome.
Time frame: 3 months, 6 months, and 12 months from primary endpoint
Durability of Response: Brief Pain Inventory (BPI) Pain Severity Score at 3, 6, and 12 Months
Brief Pain Inventory (BPI) pain severity subscale score at 3, 6, and 12 months from the primary endpoint assessment, evaluating maintenance of pain reduction over time. Scores range from 0 to 10, where 0 indicates no pain and 10 indicates pain as bad as you can imagine. Higher scores indicate worse outcome.
Time frame: 3 months, 6 months, and 12 months from primary endpoint
Durability of Response: Brief Pain Inventory (BPI) Pain Interference Score at 3, 6, and 12 Months
Brief Pain Inventory (BPI) pain interference subscale score at 3, 6, and 12 months from the primary endpoint assessment, evaluating maintenance of functional improvement over time. Scores range from 0 to 10, where 0 indicates no interference and 10 indicates complete interference with daily activities. Higher scores indicate worse outcome.
Time frame: 3 months, 6 months, and 12 months from primary endpoint
Incidence and Severity of Adverse Events
Frequency, severity, and relatedness of adverse events for each study agent (dextrose, PRP, doxycycline) and for the hyaluronic acid pathway, assessed using a standardized Adverse Event Documentation Form at every study contact. Serious adverse events are reported separately. Severity is classified as mild, moderate, or severe.
Time frame: From first injection through 12-month follow-up
Number of Treatments Required to Achieve Adequate Response
Total number of injection sessions required before a participant achieves GPI of 40% or greater, describing the treatment burden associated with the step-care approach.
Time frame: From enrollment through completion of active treatment phase, up to 12 months
No study locations are listed for this record.
Plan to share: No — This is a single-site, investigator-initiated feasibility study with no external funding and no data sharing agreement in place. Individual participant data (IPD) will not be shared with other researchers. All participants are assigned unique study ID numbers and their data are maintained under HIPAA-compliant privacy protections at Manhattan Pain Medicine. Aggregate de-identified findings will be reported through peer-reviewed publication. Future sharing of de-identified data may be considered on a case-by-case basis consistent with the IRB-approved consent form and applicable privacy regulations.
Start is estimated for Jan 2027; primary completion for Dec 2027, 11 months later.
Since we started tracking on Sep 25, 2026, the dates moved once, on Oct 6, 2026: start Jul 2026 → Jan 2027 and primary completion Sep 2027 → Dec 2027.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
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 ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Glucose · Platelet rich plasma · Doxycycline
Ehlers-Danlos syndrome type 3 →