Efficacy of intra-articular hypertonic dextrose prolotherapy versus normal saline for knee osteoarthritis: a protocol for a triple-blinded randomized controlled trial

Abstract

BackgroundKnee Osteoarthritis (KOA) is a very common condition with prevalence rising with age. It is a major contributor to global disability and has a large socioeconomic burden worldwide. Conservative therapies have marginal effectiveness, and surgery is reserved for severe symptomatic KOA. Dextrose Prolotherapy (DPT) is an evidence-based injection-based therapy for chronic musculoskeletal conditions including KOA. The standard “whole joint” injection method includes intra-articular injection and multiple extra-articular injections at soft tissue bony attachments. The procedure is painful and requires intensive procedural training often unavailable in conventional medical education, which potentially limits access. Intra-articular injection offers the possibility of a less painful, more accessible treatment. The aim of this project is to assess the clinical efficacy of intra-articular injection of DPT versus normal saline (NS) for KOA.MethodSeventy-six participants with KOA will be recruited from the community. We will conduct a single center, parallel group, superiority randomized controlled trial comparing DPT and NS injections, with blinding of physician, participants, outcome assessors and statisticians. Each group will receive injections at week 0, 4, 8 and 16. The primary outcome will be the Western Ontario McMaster University Osteoarthritis Index pain scale (WOMAC), and secondary outcomes include WOMAC composite score, the WOMAC function and stiffness subscale, the Visual Analogue Score of pain, objective physical function tests (the 30 s chair stand, 40- m fast paced walk test, the Timed up and go test) and the EuroQol-5D (EQ-5D). All outcomes will be evaluated at baseline, and 16, 26 and 52 weeks. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models.DiscussionThis paper presents the rationale, design, method and operational aspects of the trial. The findings will determine whether IA DPT, an inexpensive and simple injection, is a safe and effective non-surgical option for KOA. The results can be translated directly to clinical practice, with potentially substantial impact to patient care.Trial registrationThe trial (ChiCTR-IPC-15006617) is registered under Chinese Clinical Trials Registry on 17th June 2015.

Efficacy of Intra-Articular Hypertonic Dextrose (Prolotherapy) for Knee Osteoarthritis: A Randomized Controlled Trial

“…Details of post-injection care are in the study protocol. 24 Usual care was continued in both groups. Conventional medications, physical therapy, acupuncture, herbal medicines, over-the-counter drugs, and other active treatments were discouraged but allowed and tracked during the study period.…”

“…Sample size calculation and analysis were reported. 24 Briefly, we calculated the sample size based on the response to DPT and NS interventions in 2 RCTs. 23,38 The participants in these 2 trials had comparable baseline characteristics.…”

A Comprehensive Update of Prolotherapy in the Management of Osteoarthritis of the Knee

“…One major indication for prolotherapy is knee osteoarthritis in patients with chronic knee pain and radiographic findings of Kellgren-Lawrence stages II-IV. 14,19 Based on most recent 2019 ACR guidelines, the use of prolotherapy is in fact recommended against in patients with knee osteoarthritis citing limited number of trials, further complicated by variabilities within the methodology. 6 As recent studies have been promising, with further standardization of the approach to administering prolotherapy, guidelines will likely change to reflect the outcomes of the studies.…”

Dextrose prolotherapy for rotator cuff lesions: the challenges and the future

“…Second, it is reasonable to begin prolotherapy for RCLs using a whole joint approach with the clinical standard of 15% dextrose for extra-articular injections and 25% for intra-articular injections. 12,13 However, in time, formal assessment of different LetterS to the editor concentrations will be needed. If the aetiology of pain is mostly neuropathic, the use of 5% dextrose may be preferred.…”

“…8 Third, although there is no consensus on the optimal injection frequency, again it is reasonable to use the clinical standard of 3 to 5 injection sets 4 weeks apart followed by a booster session 8 weeks later. 12,13 Fourth, the choice of control therapy should be made with caution. Although many clinical trialists and granting agencies consider a blinded placebo injection to be necessary, normal saline injections are now understood to be active therapy.…”