A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study
Abstract Background The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer’s disease. Methods A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the effi...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13195-018-0363-1 |
| _version_ | 1819274336955006976 |
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| author | Basil H. Ridha Sebastian Crutch Dawn Cutler Christopher Frost William Knight Suzie Barker Norah Epie Elizabeth K. Warrington Riitta Kukkastenvehmas Jane Douglas Martin N. Rossor |
| author_facet | Basil H. Ridha Sebastian Crutch Dawn Cutler Christopher Frost William Knight Suzie Barker Norah Epie Elizabeth K. Warrington Riitta Kukkastenvehmas Jane Douglas Martin N. Rossor |
| author_sort | Basil H. Ridha |
| collection | DOAJ |
| description | Abstract Background The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer’s disease. Methods A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the efficacy of donepezil in patients with PCA. Each patient received either donepezil (5 mg once daily in the first 6 weeks and 10 mg once daily in the second 6 weeks) or placebo for 12 weeks. After a 2-week washout period, each patient received the other treatment arm during the following 12 weeks followed by another 2-week washout period. The primary outcome was the Mini-Mental State Examination (MMSE) at 12 weeks. Secondary outcome measures were five neuropsychological tests reflecting parieto-occipital function. Intention-to-treat analysis was used. For each outcome measure, carry-over effects were first assessed. If present, then analysis was restricted to the first 12-week period. Otherwise, the standard approach to the analysis of a 2 × 2 cross-over trial was used. Results Eighteen patients (13 females) were recruited (mean age 61.6 years). There was a protocol violation in one patient, who subsequently withdrew from the study due to gastrointestinal side effects. There was statistically significant (p < 0.05) evidence of a carry-over effect on MMSE. Therefore, the analysis of treatment effect on MMSE was restricted to the first 12-week period. Treatment effect at 6 weeks was statistically significant (difference = 2.5 in favour of donepezil, 95% CI 0.1 to 5.0, p < 0.05). Treatment effect at 12 weeks was close, but not statistically significant (difference = 2.0 in favour of donepezil, 95% CI –0.1 to 4.5, p > 0.05). There were no statistically significant treatment effects on any of the five neuropsychological tests, except for digit span at 12 weeks (higher by 0.5 digits in favour of placebo, 95% CI 0.1 to 0.9). Gastrointestinal side effects occurred most frequently, affecting 13/18 subjects (72%), and were the cause of study discontinuation in one subject. Nightmares and vivid dreams occurred in 8/18 subjects (44%), and were statistically more frequent during treatment with donepezil. Conclusions In this small study, there was no statistically significant treatment effect of donepezil on the primary outcome measure (MMSE score at 12 weeks) in PCA patients, who appear to be particularly susceptible to the development of nightmares and vivid dreams when treated. Trial registration Trial registration: Current Controlled Trials ISRCTN22636071. Retrospectively registered 19 May 2010 |
| first_indexed | 2024-12-23T23:06:49Z |
| format | Article |
| id | doaj.art-ee3912039c8e4cd7ba858e5e9ee6101a |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-23T23:06:49Z |
| publishDate | 2018-05-01 |
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| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-ee3912039c8e4cd7ba858e5e9ee6101a2022-12-21T17:26:48ZengBMCAlzheimer’s Research & Therapy1758-91932018-05-011011910.1186/s13195-018-0363-1A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD studyBasil H. Ridha0Sebastian Crutch1Dawn Cutler2Christopher Frost3William Knight4Suzie Barker5Norah Epie6Elizabeth K. Warrington7Riitta Kukkastenvehmas8Jane Douglas9Martin N. Rossor10Dementia Research Centre, UCL Institute of NeurologyDementia Research Centre, UCL Institute of NeurologyDementia Research Centre, UCL Institute of NeurologyLondon School of Hygiene and Tropical Medicine, University of LondonDementia Research Centre, UCL Institute of NeurologyDementia Research Centre, UCL Institute of NeurologyDementia Research Centre, UCL Institute of NeurologyDementia Research Centre, UCL Institute of NeurologyDementia Research Centre, UCL Institute of NeurologyDementia Research Centre, UCL Institute of NeurologyDementia Research Centre, UCL Institute of NeurologyAbstract Background The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer’s disease. Methods A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the efficacy of donepezil in patients with PCA. Each patient received either donepezil (5 mg once daily in the first 6 weeks and 10 mg once daily in the second 6 weeks) or placebo for 12 weeks. After a 2-week washout period, each patient received the other treatment arm during the following 12 weeks followed by another 2-week washout period. The primary outcome was the Mini-Mental State Examination (MMSE) at 12 weeks. Secondary outcome measures were five neuropsychological tests reflecting parieto-occipital function. Intention-to-treat analysis was used. For each outcome measure, carry-over effects were first assessed. If present, then analysis was restricted to the first 12-week period. Otherwise, the standard approach to the analysis of a 2 × 2 cross-over trial was used. Results Eighteen patients (13 females) were recruited (mean age 61.6 years). There was a protocol violation in one patient, who subsequently withdrew from the study due to gastrointestinal side effects. There was statistically significant (p < 0.05) evidence of a carry-over effect on MMSE. Therefore, the analysis of treatment effect on MMSE was restricted to the first 12-week period. Treatment effect at 6 weeks was statistically significant (difference = 2.5 in favour of donepezil, 95% CI 0.1 to 5.0, p < 0.05). Treatment effect at 12 weeks was close, but not statistically significant (difference = 2.0 in favour of donepezil, 95% CI –0.1 to 4.5, p > 0.05). There were no statistically significant treatment effects on any of the five neuropsychological tests, except for digit span at 12 weeks (higher by 0.5 digits in favour of placebo, 95% CI 0.1 to 0.9). Gastrointestinal side effects occurred most frequently, affecting 13/18 subjects (72%), and were the cause of study discontinuation in one subject. Nightmares and vivid dreams occurred in 8/18 subjects (44%), and were statistically more frequent during treatment with donepezil. Conclusions In this small study, there was no statistically significant treatment effect of donepezil on the primary outcome measure (MMSE score at 12 weeks) in PCA patients, who appear to be particularly susceptible to the development of nightmares and vivid dreams when treated. Trial registration Trial registration: Current Controlled Trials ISRCTN22636071. Retrospectively registered 19 May 2010http://link.springer.com/article/10.1186/s13195-018-0363-1Posterior cortical atrophyAlzheimer’s diseaseDonepezilClinical trial |
| spellingShingle | Basil H. Ridha Sebastian Crutch Dawn Cutler Christopher Frost William Knight Suzie Barker Norah Epie Elizabeth K. Warrington Riitta Kukkastenvehmas Jane Douglas Martin N. Rossor A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study Alzheimer’s Research & Therapy Posterior cortical atrophy Alzheimer’s disease Donepezil Clinical trial |
| title | A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study |
| title_full | A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study |
| title_fullStr | A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study |
| title_full_unstemmed | A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study |
| title_short | A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study |
| title_sort | double blind placebo controlled cross over clinical trial of donepezil in posterior cortical atrophy due to underlying alzheimer s disease donipad study |
| topic | Posterior cortical atrophy Alzheimer’s disease Donepezil Clinical trial |
| url | http://link.springer.com/article/10.1186/s13195-018-0363-1 |
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