Venlafaxine for Depression in Alzheimer's Disease (DIADs-3) (DIADs-3)

Venlafaxine for Depression in Alzheimer's Disease

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.

Study Overview

• Status: Completed
• Conditions: Depression; Alzheimer's Disease
• Intervention / Treatment: Drug: Venlafaxine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Johns Hopkins at Bayview
  • Pennsylvania
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Sugar pill	Drug: Placebo; Capsule matching active drug to be taken once a day for 12 weeks
ACTIVE_COMPARATOR: Venlafaxine; 225 mg daily over 12 weeks	Drug: Venlafaxine; 225 mg daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): January 1, 2017

Study Registration Dates

• First Submitted: April 27, 2012
• First Submitted That Met QC Criteria: May 29, 2012
• First Posted (ESTIMATE): June 1, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2018
• Last Update Submitted That Met QC Criteria: January 4, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Depression; Alzheimer's Disease
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mood Disorders; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Depression; Depressive Disorder; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
• Other Study ID Numbers: NA_00066043