Browsing by Subject "Clinical trial"

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  • Hirschfield, Gideon M.; Beuers, Ulrich; Kupcinskas, Limas; Ott, Peter; Bergquist, Annika; Färkkilä, Martti; Manns, Michael P.; Pares, Albert; Spengler, Ulrich; Stiess, Michael; Greinwald, Roland; Prols, Markus; Wendum, Dominique; Drebber, Uta; Poupon, Raoul (2021)
    Background & Aims: In patients with primary biliary cholangitis (PBC), the efficacy of budesonide, a synthetic corticosteroid displaying high first-pass metabolism, is unresolved. In a placebo-controlled, double-blind trial, we evaluated the added-value of budesonide in those with PBC and ongoing risk of progressive disease despite ursodeoxycholic acid (UDCA) treatment. Methods: We evaluated 62 patients with PBC who had histologically confirmed hepatic inflammatory activity, according to the Ishak score, and an alkaline phosphatase (ALP) >1.5x upper limit of normal (ULN), after at least 6 months of UDCA therapy. Participants were randomly assigned 2:1 to receive budesonide (9 mg/day) or placebo once daily, for 36 months, with UDCA treatment (12-16 mg/kg body weight/day) maintained. Primary efficacy was defined as improvement of liver histology with respect to inflammation and no progression of fibrosis. Secondary outcomes included changes in biochemical markers of liver injury. Results: Recruitment challenges resulted in a study that was underpowered for the primary efficacy analysis. Comparing patients with paired biopsies only (n = 43), the primary histologic endpoint was not met (p>0.05). The proportion of patients with ALP = 15% decrease in ALP and normal bilirubin was higher in the budesonide group than in the placebo group at 12, 24, and 36 months (p Conclusion: Budesonide add-on therapy was not associated with improved liver histology in patients with PBC and insufficient response to UDCA; however, improvements in biochemical markers of disease activity were demonstrated in secondary analyses. Lay summary: Around one-third of patients with primary biliary cholangitis (PBC) needs additional medical therapy alongside ursodeoxycholic acid (UDCA) treatment. In this clinical trial, the addition of the corticosteroid budesonide did not improve liver histology; there were however relevant improvements in liver blood tests. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.
  • Solomon, Alina; Handels, Ron; Wimo, Anders; Antikainen, Riitta; Laatikainen, Tiina; Levälahti, Esko; Peltonen, Markku; Soininen, Hilkka; Strandberg, Timo; Tuomilehto, Jaakko; Kivipelto, Miia; Ngandu, Tiia (2021)
    We investigated the effect of a multidomain lifestyle intervention on the risk of dementia estimated using the validated CAIDE risk score (post-hoc analysis). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a 2-year randomized controlled trial among 1,260 at-risk older adults (60-77 years). Difference in the estimated mean change in CAIDE score at 2 years in the intervention compared to the control group was -0.16 (95 % CI -0.31 to 0.00) (p = 0.013), corresponding to a relative dementia risk reduction between 6.04-6.50%. This could be interpreted as a reflection of the prevention potential of the intervention.
  • Enlund-Cerullo, Maria; Hauta-alus, Helena; Valkama, Saara; Rosendahl, Jenni; Andersson, Sture; Mäkitie, Outi; Holmlund-Suila, Elisa (2020)
    Background and objectives: Fibroblast growth factor 23 (FGF23) participates in phosphate, calcium and vitamin D metabolism. In children these interactions and modifying factors are largely unknown. Participants and methods: This study evaluates temporal changes and modifiers of FGF23 concentrations from 12 to 24 months, in healthy children, participating in a randomized vitamin D intervention (VIDI). Participants received vitamin D3 of 10 or 30 g/day from age 2 weeks to 24 months. At 12 and 24 months, growth measurements and venous blood samples were obtained for analyses of intact (iFGF23) and C-terminal FGF23 (cFGF23), 25-hydroxyvitamin D (25-OHD), calcium, phosphate, parathyroid hormone, iron and ferritin. Changes in FGF23 and modifying factors were examined by linear mixed models. Results: The study included 594 infants. Girls had higher iFGF23 than boys (p <0.001 for both 12 and 24 months), cFGF23 did not differ between the sexes. Adjusted mean iFGF23 decreased from 41.4 to 38.1 pg/mL in boys (p <0.001) and from 45.2 to 42.5 pg/mL in girls (p = 0.002). Adjusted mean cFGF23 decreased from 2.89 to 2.00 pmol/L in boys (p <0.001) and from 2.92 to 1.93 pmol/L in girls (p <0.001). Iron modified FGF23 in both sexes, associating positively with iFGF23 and inversely with cFGF23. In girls, 25-OHD modified iFGF23. In boys, season modified FGF23, possibly through seasonal differences in 25-OHD. Vitamin D intervention dose did not affect FGF23. Conclusions: FGF23 decreases from 12 to 24 months. Girls have higher iFGF23 than boys, at both time points. Iron modifies FGF23 in both sexes.
  • Giles, Francis J.; Rea, Delphine; Rosti, Gianantonio; Cross, Nicholas C. P.; Luis Steegmann, Juan; Griskevicius, Laimonas; le Coutre, Philipp; Coriu, Daniel; Petrov, Ljubomir; Ossenkoppele, Gert J.; Mahon, Francois-Xavier; Saussele, Susanne; Hellmann, Andrzej; Koskenvesa, Perttu; Bruemmendorf, Tim H.; Gastl, Gunther; Castagnetti, Fausto; Vincenzi, Beatrice; Haenig, Jens; Hochhaus, Andreas (2017)
    Purpose Achievement of deep molecular response with a tyrosine kinase inhibitor in patients with chronic myeloid leukemia (CML) is required to attempt discontinuation of therapy in these patients. The current subanalysis from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study evaluated whether age has an impact on the achievement of deeper molecular responses or safety with frontline nilotinib in patients with CML. Methods ENEST1st is an open-label, multicenter, single-arm, prospective study of nilotinib 300 mg twice daily in patients with newly diagnosed CML in chronic phase. The patients were stratified into the following 4 groups based on age: young (18-39 years), middle age (40-59 years), elderly (60-74 years), and old (>= 75 years). The primary end point was the rate of molecular response 4 ([MR4] BCR-ABL1 Results Of the 1091 patients enrolled, 1089 were considered in the analysis, of whom, 23% (n = 243), 45% (n = 494), 27% (n = 300), and 5% (n = 52) were categorized as young, middle age, elderly, and old, respectively. At 18 months, the rates of MR4 were 33.9% (95% confidence interval [CI], 27.8-40.0%) in the young, 39.6% (95% CI, 35.3-44.0%) in the middle-aged, 40.5% (95% CI, 34.8-46.1%) in the elderly, and 35.4% (95% CI, 21.9-48.9%) in the old patients. Although the incidence of adverse events was slightly different, no new specific safety signals were observed across the 4 age groups. Conclusions This subanalysis of the ENEST1st study showed that age did not have a relevant impact on the deep molecular response rates associated with nilotinib therapy in newly diagnosed patients with CML and eventually on the eligibility of the patients to attempt treatment discontinuation.
  • Koffert, Jukka; Lahti, Leo; Nylund, Lotta; Salminen, Seppo; Hannukainen, Jarna C.; Salminen, Paulina; de Vos, Willem M.; Nuutila, Pirjo (2020)
    We studied the impact of bariatric surgery on the intestinal microbiota of morbidly obese study subjects. A total of 13 morbidly obese women (five of which had type 2 diabetes) and 14 healthy age- and gender-matched controls were recruited and the microbiota composition of fecal samples were determined by using a phylogenetic microarray. Sampling of the patients took place just one month before and 6 months after the operation. Within six months after bariatric surgery, the obese subjects had lost on average a quarter of their weight whereas four of the five of the diabetic subjects were in remission. Bariatric surgery was associated with an increased microbial community richness and Bacteroidetes/Firmicutes ratio. In addition, we observed an increased relative abundance of facultative anaerobes, such as Streptococcus spp., and a reduction in specific butyrate-producing Firmicutes. The observed postoperative alterations in intestinal microbiota reflect adaptation to the changing conditions in the gastrointestinal tract, such as energy restriction and the inability to process fiber-rich foods after bariatric surgery.
  • Kuusalo, Laura; Puolakka, Kari; Kautiainen, Hannu; Karjalainen, Anna; Malmi, Timo; Yli-Kerttula, Timo; Leirisalo-Repo, Marjatta; Rantalaiho, Vappu; NEO-RACo Study Grp (2017)
    Identifying prognostic factors for remission in early rheumatoid arthritis (ERA) patients is of key clinical importance. We studied patient-reported outcomes (PROs) as predictors of remission in a clinical trial. We randomized 99 untreated ERA patients to receive remission-targeted treatment with three disease-modifying antirheumatic drugs and prednisolone for 24 months, and infliximab or placebo for the initial 6 months. At baseline, we measured following PROs: eight Short Form 36 questionnaire (SF-36) dimensions, patient's global assessment [PGA, visual analogue scale (VAS)], Health Assessment Questionnaire (HAQ), and pain VAS. We used multivariable-adjusted regression models to identify PROs that independently predicted modified American College of Rheumatology remission at 2 years. Follow-up data at 2 years were available for 93 patients (92%), and 58 patients (62%) were in remission. At baseline, patients who achieved remission had higher radiological score (p = 0.04), lower tender joint count (p = 0.001), lower PGA (p = 0.005) and physician's global assessment (p = 0.019), lower HAQ (p = 0.016), less morning stiffness (p = 0.009), and significantly higher scores in seven out of eight SF-36 dimensions compared with patients who did not. In multivariable models that included all PROs, remission was associated with SF-36 dimensions higher vitality (odds ratio 2.01; 95% confidence interval 1.19-3.39) and better emotional role functioning (odds ratio 1.64; 95% confidence interval 1.01-2.68). PGA, pain VAS, HAQ, and other SF-36 dimensions were not associated with remission. We conclude that self-reported vitality and better emotional role functioning are among the most important PROs for the prediction of remission in ERA.
  • Aspinen, Samuli; Nordback, Panu H.; Anttila, Turkka; Stjernberg-Salmela, Susanna; Ryhänen, Jorma; Kosola, Jussi (2020)
    BackgroundTrigger finger is a common hand disorder that limits finger range of motion and causes pain and snapping of the affected finger. Trigger finger is caused by an imbalance of the tendon sheath and the flexor tendon. The initial treatment is generally a local corticosteroid injection around the first annular (A1) pulley. However, it is not unusual that surgical release of the A1 pulley is required. Moreover, adverse events after local corticosteroid injection or operative treatment may occur. Platelet-rich plasma (PRP) has been shown to be safe and to reduce symptoms in different tendon pathologies, such as DeQuervain's disease. However, the effects of PRP on trigger finger have not been studied. The aim of this single-center triple-blind randomized controlled trial is to study whether PRP is non-inferior to corticosteroid injection in treating trigger finger. The secondary outcome is to assess the safety and efficacy of PRP in comparison to placebo.MethodsThe trial is designed as a randomized, controlled, patient-, investigator-, and outcome assessor-blinded, single-center, three-armed 1:1:1 non-inferiority trial. The patients with clinical symptoms of trigger finger will be randomly assigned to treatment with PRP, corticosteroid, or normal saline injection. The primary outcome is Patient-Rated Wrist Evaluation and symptom resolution. Secondary outcomes include Quick-Disabilities of the Arm, Shoulder and Hand; pain; grip strength; finger active range of motion; and complications. Appropriate statistical methods will be applied.DiscussionWe present a novel RCT study design on the use of PRP for the treatment of trigger finger compared to corticosteroid and normal saline injection. The results of the trial will indicate if PRP is appropriate for the treatment of trigger finger.Trial registrationClinicalTrials.gov NCT04167098. Registered on November 18, 2019.
  • Aspinen, Samuli; Nordback, Panu H.; Anttila, Turkka; Stjernberg-Salmela, Susanna; Ryhänen, Jorma; Kosola, Jussi (BioMed Central, 2020)
    Abstract Background Trigger finger is a common hand disorder that limits finger range of motion and causes pain and snapping of the affected finger. Trigger finger is caused by an imbalance of the tendon sheath and the flexor tendon. The initial treatment is generally a local corticosteroid injection around the first annular (A1) pulley. However, it is not unusual that surgical release of the A1 pulley is required. Moreover, adverse events after local corticosteroid injection or operative treatment may occur. Platelet-rich plasma (PRP) has been shown to be safe and to reduce symptoms in different tendon pathologies, such as DeQuervain’s disease. However, the effects of PRP on trigger finger have not been studied. The aim of this single-center triple-blind randomized controlled trial is to study whether PRP is non-inferior to corticosteroid injection in treating trigger finger. The secondary outcome is to assess the safety and efficacy of PRP in comparison to placebo. Methods The trial is designed as a randomized, controlled, patient-, investigator-, and outcome assessor-blinded, single-center, three-armed 1:1:1 non-inferiority trial. The patients with clinical symptoms of trigger finger will be randomly assigned to treatment with PRP, corticosteroid, or normal saline injection. The primary outcome is Patient-Rated Wrist Evaluation and symptom resolution. Secondary outcomes include Quick-Disabilities of the Arm, Shoulder and Hand; pain; grip strength; finger active range of motion; and complications. Appropriate statistical methods will be applied. Discussion We present a novel RCT study design on the use of PRP for the treatment of trigger finger compared to corticosteroid and normal saline injection. The results of the trial will indicate if PRP is appropriate for the treatment of trigger finger. Trial registration ClinicalTrials.gov NCT04167098 . Registered on November 18, 2019.
  • Savilahti, Erkki; Härkönen, Taina; Savilahti, Emma M.; Kukkonen, Kaarina; Kuitunen, Mikael; Knip, Mikael (2018)
  • Robinson, Jennifer G.; Farnier, Michel; Kastelein, John J. P.; Roth, Eli M.; Taskinen, Marja-Riitta; Colhoun, Helen M.; Brunet, Aurelie; DiCioccio, A. Thomas; Lecorps, Guillaume; Pordy, Robert; Baccara-Dinet, Marie T.; Cannon, Christopher P. (2019)
    BACKGROUND: Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9). OBJECTIVE: Changes in PCSK9, alirocumab, and low-density lipoprotein cholesterol (LDL-C) levels were assessed after treatment with alirocumab at doses of 75 or 150 mg every 2 weeks (Q2W). METHODS: Data were analyzed from 4 phase 3 trials (MONO; COMBO II; FH I; LONG TERM); all but MONO enrolled patients on statins. Three trials evaluated alirocumab 75 mg Q2W, with possible dose increase to 150 mg Q2W at week 12 based on week 8 LDL-C; LONG TERM studied alirocumab 150 mg Q2W. RESULTS: Patients on background statin therapy had higher mean baseline free PCSK9 concentrations vs patients not on statin. After alirocumab administration, increased alirocumab concentrations were associated with dramatic reductions in circulating free PCSK9, resulting in significant LDL-C reductions and a corresponding increase in inactive PCSK9:alirocumab complex. Alirocumab dose increase was associated with a further lowering of PCSK9 and LDL-C. Patients with higher baseline LDL-C levels (>160 mg/dL) were more likely to have their dose increased. LDL-C reductions with alirocumab were consistent between patients with baseline PCSK9 levels above or below the median when the dose increase strategy was used. When started as alirocumab 150 mg Q2W, patients with PCSK9 levels above vs below the median had a greater LDL-C reduction. CONCLUSIONS: Alirocumab-induced changes in PCSK9 and LDL-C levels were consistent with the known physiologic relationship between PCSK9, LDL receptor, and LDL-C levels, as well as statin-induced increases in PCSK9 production. (C) 2019 National Lipid Association. Published by Elsevier Inc.