Research / Projects
Video-Imaging Synthesis of Treating
Alzheimer's Disease (VISTA)
Principal Investigator: Kenneth Rockwood, MD, FRCPC, FRCP
The Video Imaging Synthesis of Treating Alzheimer’s disease (VISTA) study explored the effectiveness of treatment with galantamine from the perspectives of people living with Alzheimer’s disease and the physicians who treat them. It built upon previous randomized clinical trials which showed that people treated with galantamine performed better on clinical tests than people treated with a placebo.
The controversy around those trials - and the reason VISTA was undertaken – was that many people were skeptical about the clinical meaningfulness of drug treatment (whether statistically significant improvements on clinical tests translated into observable changes in patients that could be readily detected by physicians, family members or patients). To address this concern, the VISTA study added tests that directly assess clinical meaningfulness, in addition to the standard tests used in other drug trials.
Design and Procedures
Patients with mild-to-moderate Alzheimer’s disease were treated with either galantamine (n=64) or a placebo (n=66) for 4 months, after which all patients were treated with galantamine (total trial duration of 8 months).
Using a patient-centred method called Goal Attainment Scaling (GAS), we asked study physicians to set clinically meaningful goals for treatment. For example, a typical set of goals might judge treatment success as repeating the same question fewer times per day, showing improved initiative for social activities, misplacing objects less frequently, and showing less uncharacteristic irritability. While many goals, such as verbal repetition, were common, the actual goals set varied from patient to patient.
In addition to the goals set by doctors, patients and caregivers set their own goals (the doctors did not know which goals patients and caregivers had set, nor did they know how patients and caregivers scored their goal attainment). This was done in a semi-structured interview facilitated by an experienced clinician, usually a nurse. The nurse then made an independent assessment of how well (or poorly) patients had done (using the CIBIC+).
Goal attainment was assessed every 8 weeks. Interviews with patients and caregivers were video-recorded.
The study sample included 130 patients at baseline (63% women, 67% mild dementia, average age of 77 years), and 106 patients at the end of month 4 (galantamine group=53, placebo group=56). In general, drop-outs occurred when patients (or caregivers) withdrew their consent, stopped taking the study medication as directed, or experienced medical complications (called adverse events, usually unrelated to the study medication) that resulted in their withdrawal.
After 4 months, the patients who received galantamine did better, on average, than the patients who had taken a placebo. They scored better on a standard test of cognition (the ADAS-Cog) that all the earlier trials had used. The treating doctors also found that patients on galantamine did better on their treatment goals, improving by 5 points from their baseline score. By contrast, they found that patients who had received a placebo showed no change, on average, after 4 months of treatment. This difference was statistically significant.
Patients and caregivers also recognized a 5-point improvement in the people who took galantamine, but they also believed that patients who took placebo had done better on their goals, but only by about 3 points (not statistically significant). Interestingly though, the nurses who had facilitated the patient/caregiver goals and who were blind to what the doctors had said – and, like everyone else, to who had received galantamine and who was on placebo – also judged that patients on galantamine had done significantly better than had those on placebo.
It was also interesting that after six months – when everyone was on galantamine, but when patients on active treatment had been on the highest dose (16-24 mg/day) for at least 3 months and those who had just started treatment were not yet even taking the highest dose (8 mg/day) – all three clinical measures favored treatment with galantamine. For these reasons, we believe that, on balance, the VISTA trial showed that treatment with galantamine gives statistically significant and clinically meaningful results.
The legacy of the VISTA study is a clinical interview database that includes over 622 hours of video-recorded interviews with patients and caregivers. Those interviews, which include descriptions of dementia symptoms before and after treatment, have been qualitatively coded to identify key themes and concepts in the data. Analyses of the interview data have yielded published reports on several common, troubling, but under-studied symptoms of dementia (for example: loss of initiation, verbal repetition and misplacing). Secondary analyses of the clinical test data have also been published. Work on this rich source of patient-centred information continues.
In a recent review of 53 dementia drug trials, VISTA was highlighted as the only trial that systematically addressed the clinical meaningfulness of the effects of treating people with dementia drugs like galantamine.
VISTA was an investigator-initiated, peer-reviewed, randomized, placebo-controlled trial, conducted at 14 Canadian clinics between October 2001 and March 2005. The study was jointly funded by Janssen Ortho Inc. (the company that manufactures galantamine) and the Canadian Institutes of Health Research (grant no. DCT-49981). VISTA is registered with the International Standard Randomised Controlled Trial Number Register (ISRCTN26167328). Selected secondary analyses were funded by the Alzheimer Society of Canada (ASC grant no. 05-54).
Sherri Fay, National Study Coordinator (902-473-4575)
Attainment of treatment goals by people with Alzheimer's disease receiving galantamine: a randomized controlled trial. Rockwood K, Fay S, Song X, MacKnight C, Gorman M: VISTA Investigators. CMAJ. 2006;174:1099-1105.
Effect of galantamine on verbal repetition in AD: A secondary analysis of the VISTA trial. Rockwood K, Fay S, Jarrett P, Asp E. Neurology. 2007;68:1116-1121.
Decreased initiation of usual activities in people with mild-to-moderate Alzheimer’s disease: a descriptive analysis from the VISTA clinical trial. Cook C, Fay S, Rockwood K. Int Psychogeriatr. 2008;20:952-953.
Misplacing objects in mild to moderate Alzheimer’s disease: A descriptive analysis from the VISTA clinical trial. Hamilton L, Fay S, Rockwood K. JNNP. In press (published online 16 Mar 2009); doi:10.1136/jnnp.2008.166801.
Verbal repetition in people with mild-moderate Alzheimer's disease: A descriptive analysis from the VISTA clinical trial. Cook C, Fay S, Rockwood K. Alzheimer Dis Assoc Disord. In press (accepted 2008-09-08).
The ADAS-Cog and the detection of clinically evident change in patients with Alzheimer’s disease in the VISTA controlled trial of galantamine. Rockwood K, Fay S, Gorman M. Int J Geriatr Psychiatry. In press (accepted 2009-04-20).