The Hawthorne Effect: a randomised, controlled trial (original) (raw)
Related papers
International Journal of Geriatric Psychiatry, 2008
Objectives Doubt over the cost-effectiveness of the cholinesterase inhibitors in dementia has renewed interest in alternative treatments such as Ginkgo biloba. We aimed to determine the effectiveness and the safety profile of Ginkgo biloba for treating early stage dementia in a community setting. Methods We conducted a community-based, pragmatic, randomised, double-blind, parallel-group trial where participants were given a standardised extract of Ginkgo biloba (120 mg daily) or a placebo control for 6 months. Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD). Results We recruited 176 participants, mainly through general practices. In the ANCOVA model with baseline score as a co-variate (n ¼ 176), Ginkgo did not have a significant effect on outcome at six months on either the ADAS-Cog score ( p ¼ 0.392), the participant-rated QOL-AD score ( p ¼ 0.787) nor the carer-rated QOL-AD score ( p ¼ 0.222). Conclusion We found no evidence that a standard dose of high purity Ginkgo biloba confers benefit in mild-moderate dementia over 6 months.
International Journal of Geriatric Psychiatry, 2010
To test the efficacy and safety of a once-daily formulation of EGb 761 in the treatment of patients with dementia with neuropsychiatric features. Methods: Multi-centre trial of 410 outpatients with mild to moderate dementia (Alzheimer's disease, vascular dementia or mixed form) scoring between 9 and 23 on the SKT cognitive test battery, at least five on the Neuropsychiatric Inventory (NPI) and three or higher in at least one item of the NPI. Patients were randomly allocated to double-blind treatment with 240 mg of EGb 761 or placebo once daily for 24 weeks. Primary outcomes were the changes from baseline in the SKT total score and the NPI total score. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC), Activities of Daily Living International Scale (ADL-IS), NPI distress score, DEMQOL-Proxy quality-oflife scale and Verbal Fluency Test were secondary outcomes. Results: At endpoint, patients treated with EGb 761 (n ¼ 202) improved by À1.4 (95% confidence interval À1.8; À1.0) points on the SKT and by À3.2 (À4.0; À2.3) on the NPI total score, whereas those receiving placebo (n ¼ 202) deteriorated by þ0.3 (À0.1; 0.7) on the SKT and did not change on the NPI total score (À0.9; 0.9). Both drug-placebo comparisons were significant at p < 0.001. EGb 761 was significantly superior to placebo with respect to all secondary outcome measures. Adverse event rates were similar for both treatment groups. Conclusions: EGb 761, 240 mg once-daily, was found significantly superior to placebo in the treatment of patients with dementia with neuropsychiatric symptoms.
Ginkgo Biloba for cognitive impairment and dementia
Cochrane Database of Systematic Reviews, 2002
Background Extracts of the leaves of the maidenhair tree, Ginkgo biloba, have long been used in China as a traditional medicine for various disorders of health. A standardized extract is widely prescribed in Germany and France for the treatment of a range of conditions including memory and concentration problems, confusion, depression, anxiety, dizziness, tinnitus and headache. The mechanisms of action are thought to reflect the action of several components of the extract and include increasing blood supply by dilating blood vessels, reducing blood viscosity, modificaton of neurotransmitter systems, and reducing the density of oxygen free radicals. Objectives The aim of the review is to assess the efficacy and safety of Ginkgo biloba for the treatment of patients with dementia or cognitive decline. Search strategy Trials were identified on 26 June 2002 through a search of the CDCIG Specialized Register which contains records from all main medical databases (MEDLINE, EMBASE, CINAHL, PsycINFO, SIGLE,LILACS), from ongoing trials databases such as Clinicaltrials.gov and Current Controlled Trials and many other sources. The search terms used were ginkgo*, tanakan, EGB-761, EGB761 and "EGB 761". Selection criteria All relevant, unconfounded, randomized, double-blind controlled studies, in which extracts of Ginkgo biloba at any strength and over any period were compared with placebo for their effects on people with acquired cognitive impairment, including dementia, of any degree of severity. Data collection and analysis Data for the meta-analyses are based on reported summary statistics for each study. For the intention-to-treat analyses we sought data for each outcome measure on every patient randomized, irrespective of compliance. For the analyses of completers we sought data on every patient who completed the study on treatment. For continuous or ordinal variables, such as psychometric test scores, clinical global impression scales, and quality of life scales, there are two possible approaches. If ordinal scale data appear to be approximately normally distributed, or if the analyses reported by the investigators suggest that parametric methods and a normal approximation are appropriate, then the outcome measures will be treated as continuous variables. The second approach, which may not exclude the first, is to concatenate the data into two categories which best represent the contrasting states of interest, and to treat the outcome measure as binary. For binary outcomes, the endpoint itself is of interest and the Peto method of the typical odds ratio is used. Main results Overall, there are no significant differences between Ginkgo and placebo in the proportion of participants experiencing adverse events. Most studies report the analyses of data from participants who completed the treatment, there are few attempts at ITT analyses. Therefore we report completers analyses only. The CGI scale, measuring clinical global improvement as assessed by the physician, was dichotomized between participants who showed improvement and those who were unchanged or worse. There are benefits associated with Ginkgo (dose less than 200mg/day) compared with placebo at less than 12 weeks (54/63 showed improvement compared with 20/63, OR 15.32, 95% CI 5.90 to 39.80, P=<.0001), and Ginkgo (dose greater than 200mg/day) at 24 weeks (57/79 compared with 42/77, OR 2.16, 95% CI 1.11 to 4.20, P=.02).
2008
The epidemic of late life dementia, prominence of use of alternative medications and supplements, and initiation of efforts to determine how to prevent dementia have led to efforts to conduct studies aimed at prevention of dementia. The GEM (Ginkgo Evaluation of Memory) and GuidAge studies are ongoing randomized double-blind, placebo-controlled trials of Ginkgo biloba, administered in a dose of 120 mg twice per day as EGb761, to test whether Ginkgo biloba is effective in the prevention of dementia (and especially Alzheimer's disease) in normal elderly or those early cognitive impairment. Both GEM and GuidAge will also add substantial knowledge to the growing need for expertise in designing and implementing clinical trials to test the efficacy of putative disease-modifying agents for the dementias. While there are many similarities between GEM and Guidage, there are also significant differences. We present here the first comparative design and baseline data fromGEM and Guidage, two of the largest dementia primary prevention trials to date.
Guideline for primary care management of dementia
BMJ, 1999
Editor-Evidence based guidelines have a responsibility to consider all the relevant effective treatments and not to concentrate only on those with which clinicians are familiar. I was surprised by a serious omission from the North of England evidence based guidelines for the primary care management of dementia 1 -of category I evidence for the effectiveness of Ginkgo biloba extract in dementia, from a large randomised controlled trial. 2 The number needed to treat for a 4 point improvement in the cognitive subscale of the Alzheimer's disease assessment scale at one year of follow up has been calculated as 7.9 (95% confidence interval 4.2 to 67); for a significant improvement in the geriatric assessment by relative's rating instrument (a daily living and social behaviour score assessed by family members) it was 7.0 (3.3 to 97). The dose of G biloba extract was 120 mg a day. G biloba extract is available over the counter, and the cost of a year's treatment (from one major supermarket) is £85. A year's treatment with donepezil, by contrast, costs £891 for 5 mg and £1248 for 10 mg.
Neuropsychiatric Disease and Treatment, 2011
To examine the effects of Ginkgo biloba extract EGb 761 ® on neuropsychiatric symptoms of dementia. Patients and methods: Randomized, controlled, double-blind, multicenter clinical trial involving 410 outpatients with mild to moderate dementia (Alzheimer's disease with or without cerebrovascular disease, vascular dementia), scoring at least 5 on the Neuropsychiatric Inventory (NPI), with at least one item score of 3 or more. Total scores on the SKT cognitive test battery (Erzigkeit's short syndrome test) were between 9 and 23. After random allocation, the patients took 240 mg of EGb 761 ® or placebo once daily for a period of 24 weeks. Changes from baseline to week 24 in the NPI composite and in the SKT total score were the primary outcomes. The NPI distress score was chosen as a secondary outcome measure to evaluate caregivers' distress. Results: The NPI composite score improved by −3.2 (95% confidence interval −4.0 to −2.3) in patients taking EGb 761 ® (n = 202), but did not change (−0.9; 0.9) in those receiving placebo (n = 202), which resulted in a statistically significant difference in favor of EGb 761 ® (P , 0.001). Treatment with EGb 761 ® was significantly superior to placebo for the symptoms apathy/indifference, sleep/night-time behavior, irritability/lability, depression/dysphoria, and aberrant motor behavior. Caregivers' distress evaluation revealed similar baseline pattern and improvements. Conclusion: Treatment with EGb 761 ® , at a once-daily dose of 240 mg, was safe, effectively alleviated behavioral and neuropsychiatric symptoms in patients with mild to moderate dementia, and improved the wellbeing of their caregivers.
The Lancet Neurology, 2012
Background Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess effi cacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. Methods In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510. Findings Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1•2 cases per 100 person-years) compared with 73 participants in the placebo group (1•4 cases per 100 person-years; hazard ratio [HR] 0•84, 95% CI 0•60-1•18; p=0•306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0•94, 0•69-1•28; p=0•68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1•12, 95% CI 0•77-1•63; p=0•57). Incidence of other haemorrhagic or cardiovascular events also did not diff er between groups. Interpretation Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. Funding Ipsen.
Effects of Ginkgo biloba on dementia: An overview of systematic reviews
Objective: To assess the cumulative evidence on the efficacy and effectiveness of Ginkgo biloba extract (GbE) in the treatment of dementia. Design: Overview of systematic reviews. Methods: PubMed/MEDLINE, EMBASE, Cochrane, and Google Scholar were searched in June 2016. Systematic reviews (SRs) of randomized controlled trials (RCTs) evaluating the effects of GbE on different outcomes in people with dementia or cognitive impairment were included. Methodological quality of the included SRs was assessed using the AMSTAR tool. The quality of evidence of the primary studies was assessed using GRADE. Results: Twelve SRs with meta-analyses met the eligibility criteria. The quality of the evidence reported in these SRs varies ranging from low to moderate level. Overall, the available evidence suggests that GbE has potentially beneficial effects over placebo on cognitive performance, activities of daily living, and clinical global impression in the treatment of dementia at doses greater than 200 mg/day (usually 240 mg/day) administrated for 22 weeks or longer, and that GbE appears to be safe for human consumption. No sufficient evidence supports the favorable effects of GbE administrated for less than 22 weeks. The available evidence consistently indicates that a dose less than 200 mg/day of GbE may not be adequate to yield clinical relevant effects in the treatment of dementia.