Dalhousie University
   

   
 


Research / Projects
Video-Imaging Synthesis of Treating
Alzheimer's Disease (VISTA)

Principal Investigator:  Kenneth Rockwood, MD, FRCPC, FRCP

Background

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.

Results

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.

Current work

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.

Funding

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).

Contact

Sherri Fay, National Study Coordinator  (902-473-4575)

Further Readings

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).

 

 

 
   
 
 
Cognition: a higher level of brain function that includes, for example, memory, reasoning, judgment and awareness  
Placebo-controlled: a clinical trial design in which one group of people is used as a comparison group (a control) for another group; the control group is similar to the test group, but they do not receive the same therapy
Peer-reviewed: a review wherein people working in the same field (in this cases, other physicians) evaluate a study protocol (before a study begins) or a study report (after the study has been conducted) to ensure the work is of sufficient quality and integrity 
Investigator-initiated: research that is proposed by an independent investigator, usually a physician, rather than a pharmaceutical company
Qualitative: a distinction based on quality or characteristic rather than quantity, often subjective
Clinical measures: a term used to refer to assessments or evaluations based on clinical judgment (subjective)
ADAS-Cog: Alzheimer’s Disease Assessment Scale–cognitive subscale; a cognitive test used in clinical trials of dementia
Consent: people who participate in clinical trials must provide written informed consent indicating that they have received adequate information about the trial (what the trial is for, what they are being asked to do, the potential risks and benefits) and freely agree to participate
Adverse events: a negative change in health that occurs while a person is participating in a clinical trial that may or may not be a side-effect of the treatment under study
Drop-outs: study participants who do not complete the full course of a clinical trial (eg, stop participating after week 3 of an 8 week trial)
Baseline: the evaluations made at a baseline visit (before any study treatments have been started) are the measuring stick to which post-baseline (post-treatment) evaluations are compared
CIBIC+: Clinician’s Interview-Based Impression of Change–plus caregiver input; a semi-structured interview used in clinical trials to assess change based on global clinical observations
Goal Attainment Scaling: a method of evaluating whether a treatment or intervention meets goals that are meaningful and specific to the person receiving the intervention
Patient-centred: the idea that the individual being treated should have a say in their own health care decisions and evaluations of efficacy, and that important health outcomes may not be the same for all patients (one size does not fit all)
Statistically significant: differences between groups that are unlikely to have occurred by chance
Clinical meaningfulness: a result or outcome that is considered to be worthwhile or clinically important
Placebo: a sugar pill with no active ingredient that looks and tastes just like the active study medication
Randomized: when there is no specific pattern that determines treatment group assignments; participants can be said to have an equal chance of be assigned to any treatment group (like the flip of a coin)
Galantamine: an anti-dementia medication, also called Reminyl®, used to treat the symptoms of mild and moderate Alzheimer’s disease
Dalhousie University Faculty of Medicine