The Current Status of Clinical Trials on Biologics for Cartilage Repair and Osteoarthritis Treatment: An Analysis of ClinicalTrials.gov Data

Zhang, Zijun; Schon, Lew C.

doi:10.1177/19476035221093065

Cited by 11 publications

(5 citation statements)

References 58 publications

(63 reference statements)

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“…Our data also displayed that the rate of registered trials not achieving publication was alarmingly high (73%), even when compared with publication rates of clinical trials related to orthopedic trauma (43%), 51 biologics for cartilage repair and osteoarthritis (44%), 52 and adult spine surgery (21%). 50 Nonetheless, it is noteworthy that 19.2% of the trials included in the analysis were flagged as completed but lacked any reported results, potentially indicating a concern for publication bias.…”

Section: Discussionmentioning

confidence: 79%

Why clinical trials in disc regeneration strive to achieve completion: Insights from publication status and funding sources

Ambrosio,

Petrucci,

Russo

et al. 2024

JOR Spine

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BackgroundChronic discogenic low back pain (LBP) poses a significant global burden, yet effective therapeutic interventions directly targeting the underlying degenerative process remain elusive. After demonstrating promising results in preclinical studies, intradiscal injection of cell‐based treatments has been increasingly investigated in the clinical setting. However, most clinical trials failed to reach publication, with the few available reports showing only minor improvements. The aim of this study was to analyze the prospective clinical trials registered on ClinicalTrials.gov investigating cell therapies for LBP, with a specific emphasis on identifying critical obstacles hindering study completion, including trial design and funding sources.MethodsA systematic search of prospective clinical trials investigating cell‐based treatments for chronic LBP due to intervertebral disc degeneration was performed on ClinicalTrials.gov. Extracted data encompassed study design, recruitment, experimental treatment modalities, investigated outcomes, current status, completion date, publication status, and funding sources. Fisher's exact test assessed associations between categorical variables, while a multiple logistic regression model aimed to identify factors potentially linked to the publication status of the studies.ResultsOur search identified 26 clinical trials. Among these, only 7 (26.9%) were published, and none of the other studies marked as completed reported any results on ClinicalTrials.gov. Fifty percent of included trials were funded by universities, whereas the rest was sponsored by industry (38.5%) or private institutions (11.5%). Experimental treatments primarily involved cell‐based or cell‐derived products of varying sources and concentrations. Products containing carriers, such as hyaluronic acid or fibrin, were more frequently funded by industry and private organizations (p = 0.0112). No significant differences emerged when comparing published and nonpublished studies based on funding, as well as between publication status and other variables.ConclusionMost clinical trials exploring cell‐based disc regenerative therapies for chronic LBP have never reached completion, with only a small fraction reporting preliminary data in publications.

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Section: Discussionmentioning

confidence: 79%

Why clinical trials in disc regeneration strive to achieve completion: Insights from publication status and funding sources

Ambrosio,

Petrucci,

Russo

et al. 2024

JOR Spine

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“…Joinpoint regression fits a piecewise linear regression model, which is a special case of linear spline [ 13 ]. Early phase 1, phase 1, and phase 2 were combined as early phase, and phases 3 and 4 were combined as advanced phase [ 14 ]. The median age of each trial was compared with the median age of the relevant disease site according to the NCI Surveillance, Epidemiology, and End Results (SEER) database [ 9 , 15 ].…”

Section: Methodsmentioning

confidence: 99%

The current status of clinical trials on cancer and age disparities among the most common cancer trial participants

Zhao,

Miao,

Wang

et al. 2024

BMC Cancer

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Objective To illustrate the status of all cancer clinical trials and characterize clinical trial enrollment disparities in the most common cancer. Methods Clinical trial data were extracted from ClinicalTrials.gov website. All searched clinical trials were included in the current status analysis of clinical trials on cancer. Among all the clinical trials, only trials addressing single disease sites of breast, prostate, colorectal, or lung (BPCRL) cancer were included in the age disparities analysis. The difference in median age (DMA) between the trial participant median age and the population-based disease-site-specific median age was calculated for each trial. Results A total of 7747 clinical trials were included in the current status analysis of clinical trials on cancer. The number of registered trials had been increasing from 2008 to 2021 (AAPC = 50.60, 95% CI 36.60, 66.00, P < 0.05). Of the 7747 trials, 1.50% (116) of the studies were clinical trials for the elderly aged 60 years or older. 322 trials were included in the age disparities analysis. For all trials, the median DMA was − 8.15 years (P25, P75, − 10.83 to − 2.98 years, P < 0.001). The median DMA were − 9.55 years (P25, P75, − 11.63 to − 7.11 years), − 7.10 years (P25, P75, − 9.80 to − 5.70 years), − 9.75 years (P25, P75, − 11.93 to − 7.35 years), 3.50 years (P25, P75, 0.60 to 4.55 years), respectively, for breast cancer, colorectal cancer, lung cancer and prostate cancer. Conclusion The numbers of registered clinical trials show an upward trend. Age disparities between trial participants and diagnosed disease population are present in BPCRL cancer trials and appear to be increasing over time. Equitable participation in clinical trials on the basis of age is crucial for advancing medical knowledge and evaluating the safety and efficacy of new treatments that are generalizable to aging populations.

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“…Recently, mesenchymal stromal cells (MSCs) have emerged as a promising treatment for OA 11 – 14 . More than two hundred related clinical trials have been registered at the clinicaltrials.gov 15 . However, the outcomes have been heterogenous and the effects do not last long 16 .…”

Section: Introductionmentioning

confidence: 99%

Comparison studies identify mesenchymal stromal cells with potent regenerative activity in osteoarthritis treatment

Chu,

Zhang,

Zhang

et al. 2024

npj Regen Med

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Osteoarthritis affects 15% of people over 65 years of age. It is characterized by articular cartilage degradation and inflammation, leading to joint pain and disability. Osteoarthritis is incurable and the patients may eventually need joint replacement. An emerging treatment is mesenchymal stromal cells (MSCs), with over two hundred clinical trials being registered. However, the outcomes of these trials have fallen short of the expectation, due to heterogeneity of MSCs and uncertain mechanisms of action. It is generally believed that MSCs exert their function mainly by secreting immunomodulatory and trophic factors. Here we used knee osteoarthritis mouse model to assess the therapeutic effects of MSCs isolated from the white adipose or dermal adipose tissue of Prrx1-Cre; R26tdTomato mice and Dermo1-Cre; R26tdTomato mice. We found that the Prrx1-lineage MSCs from the white adipose tissues showed the greatest in vitro differentiation potentials among the four MSC groups and single cell profiling showed that the Prrx1-lineage MSCs contained more stem cells than the Dermo1 counterpart. Only the Prrx1-lineage cells isolated from white adipose tissues showed long-term therapeutic effectiveness on early-stage osteoarthritis models. Mechanistically, Prrx1-lineage MSCs differentiated into Col2+ chondrocytes and replaced the damage cartilage, activated Col1 expressing in resident chondrocytes, and inhibited synovial inflammation. Transcriptome analysis showed that the articular chondrocytes derived from injected MSCs expressed immunomodulatory cytokines, trophic factors, and chondrocyte-specific genes. Our study identified a MSC population genetically marked by Prrx1 that has great multipotentiality and can differentiate into chondrocytes to replace the damaged cartilage.

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The Current Status of Clinical Trials on Biologics for Cartilage Repair and Osteoarthritis Treatment: An Analysis of ClinicalTrials.gov Data

Cited by 11 publications

References 58 publications

Why clinical trials in disc regeneration strive to achieve completion: Insights from publication status and funding sources

Why clinical trials in disc regeneration strive to achieve completion: Insights from publication status and funding sources

The current status of clinical trials on cancer and age disparities among the most common cancer trial participants

Comparison studies identify mesenchymal stromal cells with potent regenerative activity in osteoarthritis treatment

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