Regenerative Medicine for Joint Hypermobility and Instability

Summary

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.

Conditions

• Subluxation
• Dislocation
• Ehlers-Danlos Syndrome Hypermobility Type (hEDS)
• Ehlers-Danlos Syndrome (EDS)
• Joint Hypermobility
• Joint Instability
• Hypermobility Spectrum Disorder
• Chronic Pain Syndrome
• Musculoskeletal Pain
• Sprain
• Craniocervical Disfunction

Interventions

DRUG

Dextrose 20% Prolotherapy

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.

BIOLOGICAL

Autologous Platelet-Rich Plasma

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.

DRUG

Doxycycline Hyclate Injectable (Investigational)

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.

DEVICE

Visco-3 Sodium Hyaluronate Viscosupplementation

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.

Sponsors & Collaborators

• Manhattan Pain Medicine, PLLC

  lead OTHER

Principal Investigators

• Jason Siefferman, MD · Manhattan Pain Medicine

• Mariia Safroshkina, MD · Manhattan Pain Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-07-15

Primary Completion

2027-09-30

Completion

2028-12-31

FDA Drug

Yes

FDA Device

Yes