Frailty, a syndrome that decreases healthspan in older individuals, lacks effective therapies. We conducted a randomized, dose-finding clinical trial to test whether human bone marrow-derived allogeneic mesenchymal stem cells (MSCs; laromestrocel) improve physical functioning and patient self-reported outcomes in ambulatory individuals with frailty (ClinicalTrials.gov #NCT03169231; N = 148). Laromestrocel infusion results in clinically meaningful, dose- and time-dependent increases in the 6-min walk test (6MWT; primary endpoint) compared with placebo: 63.4 m (95% confidence interval [CI]: 17.1-109.6 m; p = 0.0077) at month 9 and 41.3 m (95% CI: -2.4-84.9 m; p = 0.0635) at month 6. Increased 6MWT distance correlates with PROMIS Physical Function score, and increasing doses of laromestrocel are associated with decreases in soluble (degraded) tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE2), the cognate receptor for the angiopoietins, identifying a potential biomarker of laromestrocel responsiveness. These findings identify a stem cell therapy approach for the management of patients with hypomobility and other features of aging frailty.
BACKGROUND:Nasolabial folds (NLFs) are common age-related facial lines, often treated with dermal fillers. Princess FILLER Lidocaine (PFL; now saypha filler Lidocaine) and Juvéderm Ultra XC (JUXC) are both hyaluronic acid-based fillers used for this purpose. OBJECTIVES:The aim of the authors of this study is to evaluate the effectiveness and safety of PFL in reducing NLF severity compared with JUXC using a split-face study design. METHODS:In this randomized, subject- and investigator-blinded multicenter study, patients with moderate-to-severe NLFs received PFL on one side of the face and JUXC on the other. Baseline NLF severity was assessed using the 5-point NLF-Severity Rating Scale (NLF-SRS). Follow-up assessments occurred at Weeks 12, 24, 36, and/or 48. The primary endpoint was the proportion of NLF-SRS responders at Week 24. Secondary endpoints included assessments by photographic reviewers and treating investigators, along with Global Aesthetic Improvement Scale (GAIS) ratings. Safety was monitored by adverse event reporting and patient diaries. FACE-Q questionnaires evaluated patient satisfaction. Repeat treatment was permitted at Week 36 or 48 if needed. RESULTS:At Week 24, PFL demonstrated noninferiority to JUXC (82.2% vs 81.9% responders; difference 0.37%, P < .0001). Secondary assessments confirmed this finding. Adverse events occurred in 24.4% of patients post PFL, with most being mild to moderate. Serious treatment-emergent adverse events were rare (1.1%). CONCLUSIONS:PFL is a noninferior alternative to JUXC for treating moderate-to-severe NLFs, with comparable efficacy, safety, and patient satisfaction. LEVEL OF EVIDENCE: 1 (THERAPEUTIC):For image description, please refer to the figure legend and surrounding text.
Current topical treatments for scalp psoriasis are limited by formulation, efficacy, and/or safety. To assess safety and efficacy of roflumilast foam, 0.3%, in patients with psoriasis of the scalp and body. This was a phase 3 double-blinded, vehicle-controlled randomized clinical trial conducted between August 24, 2021, and June 3, 2022, at 49 sites in Canada and the US. Eligible participants were 12 years and older with plaque psoriasis affecting up to 25% of the scalp and body, at least 10% of the scalp, and up to 20% of nonscalp areas, with a minimum Scalp−Investigator Global Assessment (S-IGA) score of 3 (moderate), and minimum Body−IGA (B-IGA) score of 2 (mild). Data analyses were performed from September 9 to December 30, 2022. Once-daily roflumilast foam, 0.3%, or vehicle for 8 weeks. Coprimary end points were S-IGA and B-IGA success (clear [0] or almost clear [1] plus ≥2-grade improvement) at week 8. Secondary end points included S-IGA success at weeks 2 and 4, change in Scalp Itch−Numeric Rating Scale (SI-NRS), and SI-NRS and Worst Itch−NRS (WI-NRS) success (≥4-point improvement in patients with baseline score of ≥4). Safety and tolerability were also assessed. A total of 432 patients (mean [SD] age, 47.3 [14.8] years; 243 women [56.3%]) were randomized to roflumilast foam (n = 281) or vehicle (n = 151). At week 8, 66.4% of the roflumilast group achieved S-IGA success vs 27.8% of the vehicle group (P < .001); and 45.5% of the roflumilast group achieved B-IGA success compared with 20.1% of the vehicle group (P < .001). Rates for S-IGA success at week 2 and SI-NRS and WI-NRS success at weeks 2, 4, and 8 were significantly higher for roflumilast vs vehicle. Improvements in SI-NRS were greater for the roflumilast vs the vehicle group as early as the first assessment (24 hours after the first application). Both study groups had low rates of adverse events and favorable tolerability profiles. This randomized clinical trial found that roflumilast foam, 0.3%, improved signs and symptoms of psoriasis on the scalp and body, including pruritus, with low rates of adverse events in patients 12 years and older. These results demonstrate the potential of roflumilast foam, 0.3%, as monotherapy for patients with psoriasis of the scalp and body. ClinicalTrials.gov Identifier: NCT05028582
DTMTM programming differentially modulate neurons and glia to balance interactions perturbed by neuropathic pain in preclinical studies. DTM spinal cord stimulation (SCS) provide significant back pain relief in patients in a feasibility trial. Here, we report a large randomized controlled trial (RCT) comparing the effectiveness of DTM SCS to traditional SCS.
DTMTM SCS is a programming approach where electrical signals are multiplexed spatially and temporally. We report data from a RCT comparing the effectiveness of DTM SCS to traditional SCS for low back pain (LBP) relief. At the 12-month follow-up, a high number of subjects experience profound LBP relief (≥ 80%) with DTM SCS. A sub-analysis of profound LBP responders was conducted.
