Alzheimer's Disease, Depression
Conditions
Keywords
Depression, Alzheimer's Disease
Brief summary
This study will test the use of venlafaxine to treat the depression in Alzheimer's Disease. Venlafaxine works by increasing natural substances in the brain (serotonin and norepinephrine) that help maintain mental balance. Alzheimer's disease (AD) is the commonest neurodegenerative disease of aging and the cause of major financial and emotional burden to patients, families and caregivers, and society. Depression is a very common symptom of AD, affecting as many as 50% of patients over their illness. Depression in AD (Alzheimer's disease) contributes greatly to patient disability and caregiver distress. Neither psychosocial interventions nor psychotropic medications have proven effective to date for the treatment of depression in AD.Venlafaxine is approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depression but it is not known whether or not it can help depression in Alzheimer's Disease.
Interventions
DRUGPlacebo
Capsule matching active drug to be taken once a day for 12 weeks
DRUGVenlafaxine
225 mg daily for 12 weeks
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Dementia due to Alzheimer's disease by Diagnostic and Statistical Manual Diploma in Social Medicine (DSM)-IV (TR) criteria (90), with a Mini-Mental State Exam (MMSE) (82) score of 10-26 inclusive; * Depression as defined by the National Institute of Mental Health (NIMH) Consensus Criteria, * Clinical Dementia Rating Scale of 1 mild or 2 moderate. Ratings of 3 severe will be excluded because many of the instruments lack validity in the presence of severe cognitive impairment, particularly language deficits. * Sufficiently good health to be treated using the study protocol in usual care circumstances; * Patient or surrogate and caregiver provides informed consent for participation in the study; * A caregiver is available who spends at least 10 hours per week with the patient, supervises her care, and is willing to accompany the patient to study visits and to provide information about the patient. * Female participants must be at least 2 years post menopause or surgically sterilized.
Exclusion criteria
* Presence of a brain disease that might otherwise fully explain the presence of dementia, such as stroke, Parkinson's disease, traumatic brain injury, multiple sclerosis, and similar neurologic diseases; * Clinically significant psychosis that requires antipsychotic treatment; -Treatment with venlafaxine is contraindicated in the opinion of the attending psychiatrist, for example if there is a prior history of dangerous or -unacceptable side effects when treated with venlafaxine; * Failure of treatment with venlafaxine in the past for depression after convincing evidence of a good trial, for example 8 weeks at the highest tolerated dose; * Treatment for a condition or with a medication that would prohibit the safe concurrent use of venlafaxine (specifically including systolic blood pressure \> 180 mm Hg or diastolic blood pressure \> 100 mm Hg); * Diagnosis of congenital long Q-T syndrome * The patient requires psychiatric hospitalization for depression or is suicidal; * Initiation, discontinuation or dose changes in cholinesterase inhibitor or memantine use within the 4 weeks prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Dose Response Using the Modified Alzheimer's Disease (AD) Cooperative Study-Clinical Global Impression of Change. | 12 weeks | Treatment will be considered efficacious if the proportion of worse categories (including 'minimal worsening', 'moderate worsening', or 'marked worsening') is lower under treatment than control on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. Clinical Global Impression of Change: This is a 7-item score ranging from markedly worse to markedly improved. It is assessed by the study clinician who interviews both participant and informant and makes an informed judgment how to incorporate their input |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Venlafaxine 225 mg daily over 12 weeks
Venlafaxine: 225 mg daily for 12 weeks | 3 |
| Sugar Pill Placebo: Capsule matching active drug to be taken once a day for 12 weeks | 2 |
| Total | 5 |
Baseline characteristics
| Characteristic | Venlafaxine | Sugar Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 1 / 3 | 1 / 2 |
| serious Total, serious adverse events | 1 / 3 | 0 / 2 |
Outcome results
Primary
Changes in Dose Response Using the Modified Alzheimer's Disease (AD) Cooperative Study-Clinical Global Impression of Change.
Treatment will be considered efficacious if the proportion of worse categories (including 'minimal worsening', 'moderate worsening', or 'marked worsening') is lower under treatment than control on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. Clinical Global Impression of Change: This is a 7-item score ranging from markedly worse to markedly improved. It is assessed by the study clinician who interviews both participant and informant and makes an informed judgment how to incorporate their input
Time frame: 12 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Venlafaxine | Changes in Dose Response Using the Modified Alzheimer's Disease (AD) Cooperative Study-Clinical Global Impression of Change. | Marked improvement according to CGI | 2 Participants |
| Venlafaxine | Changes in Dose Response Using the Modified Alzheimer's Disease (AD) Cooperative Study-Clinical Global Impression of Change. | Moderate improvement according to CGI | 1 Participants |
| Sugar Pill | Changes in Dose Response Using the Modified Alzheimer's Disease (AD) Cooperative Study-Clinical Global Impression of Change. | Marked improvement according to CGI | 0 Participants |
| Sugar Pill | Changes in Dose Response Using the Modified Alzheimer's Disease (AD) Cooperative Study-Clinical Global Impression of Change. | Moderate improvement according to CGI | 2 Participants |