Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study.

ObjectiveTo assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA).MethodsPatients with Morquio A aged ≥5 years (N = 176) were randomised (1:1:1) to receive elosulfase alfa 2.0 mg/kg/every other week (qow), elosulfase alfa 2.0 mg/kg/week (weekly) or placebo for 24 weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated.ResultsAt week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95 % CI 4.0, 40.9; P = 0.017) for weekly and 0.5 m (95 % CI -17.8, 18.9; P = 0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95 % CI -2.1, 4.4; P = 0.494) for weekly and -0.5 stairs/min (95 % CI -3.7, 2.8; P = 0.778) for qow. Normalised urine KS was reduced at 24 weeks in both regimens. In the weekly dose group, 22.4 % of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3 % of all infusions in this group) over 6 months. No adverse events led to permanent treatment discontinuation.ConclusionsElosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile

A randomised controlled trial evaluating family mediated exercise (FAME) therapy following stroke

<p>Abstract</p> <p>Background</p> <p>Stroke is a leading cause of disability among adults worldwide. Evidence suggests that increased duration of exercise therapy following stroke has a positive impact on functional outcome following stroke. The main objective of this randomised controlled trial is to evaluate the impact of additional family assisted exercise therapy in people with acute stroke.</p> <p>Methods/Design</p> <p>A prospective multi-centre single blind randomised controlled trial will be conducted. Forty patients with acute stroke will be randomised into either an experimental or control group. The experimental group will receive routine therapy and additional lower limb exercise therapy in the form of family assisted exercises. The control group will receive routine therapy with no additional formal input from their family members. Participants will be assessed at baseline, post intervention and followed up at three months using a series of standardised outcome measures. A secondary aim of the project is to evaluate the impact of the family mediated exercise programme on the person with stroke and the individual(s) assisting in the delivery of exercises using a qualitative methodology. The study has gained ethical approval from the Research Ethics Committees of each of the clinical sites involved in the study.</p> <p>Discussion</p> <p>This study will evaluate a structured programme of exercises that can be delivered to people with stroke by their 'family members/friends'. Given that the progressive increase in the population of older people is likely to lead to an increased prevalence of stroke in the future, it is important to reduce the burden of this illness on the individual, the family and society. Family mediated exercises can maximise the carry over outside formal physiotherapy sessions, giving patients the opportunity for informal practice.</p> <p>Trial Registration</p> <p>The protocol for this study is registered with the US NIH Clinical trials registry (NCT00666744)</p

Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy

<p>Abstract</p> <p>Background</p> <p>Chronic fatigue syndrome (CFS, also called myalgic encephalomyelitis/encephalopathy or ME) is a debilitating condition with no known cause or cure. Improvement may occur with medical care and additional therapies of pacing, cognitive behavioural therapy and graded exercise therapy. The latter two therapies have been found to be efficacious in small trials, but patient organisations' surveys have reported adverse effects. Although pacing has been advocated by patient organisations, it lacks empirical support. Specialist medical care is commonly provided but its efficacy when given alone is not established. This trial compares the efficacy of the additional therapies when added to specialist medical care against specialist medical care alone.</p> <p>Methods/Design</p> <p>600 patients, who meet operationalised diagnostic criteria for CFS, will be recruited from secondary care into a randomised trial of four treatments, stratified by current comorbid depressive episode and different CFS/ME criteria. The four treatments are standardised specialist medical care either given alone, or with adaptive pacing therapy or cognitive behaviour therapy or graded exercise therapy. Supplementary therapies will involve fourteen sessions over 23 weeks and a 'booster session' at 36 weeks. Outcome will be assessed at 12, 24, and 52 weeks after randomisation. Two primary outcomes of self-rated fatigue and physical function will assess differential effects of each treatment on these measures. Secondary outcomes include adverse events and reactions, subjective measures of symptoms, mood, sleep and function and objective measures of physical activity, fitness, cost-effectiveness and cost-utility. The primary analysis will be based on intention to treat and will use logistic regression models to compare treatments. Secondary outcomes will be analysed by repeated measures analysis of variance with a linear mixed model. All analyses will allow for stratification factors. Mediators and moderators will be explored using multiple linear and logistic regression techniques with interactive terms, with the sample split into two to allow validation of the initial models. Economic analyses will incorporate sensitivity measures.</p> <p>Discussion</p> <p>The results of the trial will provide information about the benefits and adverse effects of these treatments, their cost-effectiveness and cost-utility, the process of clinical improvement and the predictors of efficacy.</p

Efficacy of tibolone and raloxifene for the maintenance of skeletal muscle strength, bone mineral density, balance, body composition, cognitive function, mood/depression, anxiety and quality of life/well-being in late postmenopausal women ≥ 70 years: Study design of a randomized, double-blind, double-dummy, placebo-controlled, single-center trial

<p>Abstract</p> <p>Background</p> <p>Postmenopausal women are prone to develop functional disabilities as a result of reduction in muscle strength and muscle mass caused by diminished levels of female sex hormones. While hormone replacement therapy may counteract these changes, conventional hormone replacement therapy is associated with potential harmful effects, such as an increased risk of breast cancer, and its prescription is not recommended. For this reason newer alternative drugs, such as tibolone, a synthetic steroid with estrogenic, progestogenic and androgenic activity, and raloxifene, a selective estrogen receptor modulator, may be more appropriate. This trial investigates the effect of tibolone and raloxifene on muscle strength.</p> <p>Methods</p> <p>We recruited 318 elderly women in our single-center randomized, double-blind, double-dummy, placebo-controlled trial. Participants were randomized to tibolone 1.25 mg (Org OD 14, Organon NV, the Netherlands) plus placebo, raloxifene 60 mg (Evista^®, Eli Lilly, United States) plus placebo or two placebo tablets daily for 24 months.</p> <p>The primary aim is to determine if there is a difference between tibolone and placebo or if there is a difference between raloxifene and placebo. Primary endpoints are muscle strength and bone mineral density. The secondary endpoints are postural balance, body composition, cognitive function, anxiety, mood and quality of life. The secondary aim is to determine if there is a difference between tibolone and raloxifene.</p> <p>The measure of effect is the change from the baseline visit to the visits after 3 months, 6 months, 12 months, and 24 months. A follow-up measurement is planned at 30 months to determine whether any effects are sustained after cessation of the study. By December 2007 the blind will be broken and the data analyzed.</p> <p>Trial registration number</p> <p>NTR: 1232</p

Outcome measures in chronic obstructive pulmonary disease (COPD): strengths and limitations

Current methods for assessing clinical outcomes in COPD mainly rely on physiological tests combined with the use of questionnaires. The present review considers commonly used outcome measures such as lung function, health status, exercise capacity and physical activity, dyspnoea, exacerbations, the multi-dimensional BODE score, and mortality. Based on current published data, we provide a concise overview of the principles, strengths and weaknesses, and discuss open questions related to each methodology. Reviewed is the current set of markers for measuring clinically relevant outcomes with particular emphasis on their limitations and opportunities that should be recognized when assessing and interpreting their use in clinical trials of COPD