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.
Adults age 18 years or older, any gender.
hEDS diagnosed using the 2017 International Classification of the Ehlers-Danlos Syndromes diagnostic criteria;
HSD classified using the 2017 framework (generalized, peripheral, localized, or historical HSD) with Beighton scoring; or
post-traumatic joint instability with ligamentous injury documented by examination and/or imaging.
Impaired decision-making capacity that precludes valid informed consent.
Active local or systemic infection.
Known allergy or contraindication to study injections, local anesthetics, iodinated contrast (if fluoroscopy is planned), or required procedural materials.
Known hypersensitivity or intolerance to tetracycline-class antibiotics, including doxycycline (relevant to the doxycycline treatment phase).