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

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01609348
• Collaborator: (none)
• Enrollment: 5
• Locations: 2
• Arms: 2
• Duration (Months): 57
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease; Depression	Drug: Placebo; Drug: Venlafaxine	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Venlafaxine for Depression in Alzheimer's Disease
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins at Bayview	Baltimore	Maryland	United States	21225
2	Reading Hospital	West Reading	Pennsylvania	United States	19611

Sponsors and Collaborators

• Johns Hopkins University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01609348
• Other Study ID Numbers: NA_00066043
• First Posted: Jun 1, 2012
• Last Update Posted: Jan 31, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Johns Hopkins University: Depression; Alzheimer's Disease
• Additional relevant MeSH terms: Alzheimer Disease; Depression; Depressive Disorder; Venlafaxine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Venlafaxine	Sugar Pill
Arm/Group Description	225 mg daily over 12 weeks Venlafaxine: 225 mg daily for 12 weeks	Placebo: Capsule matching active drug to be taken once a day for 12 weeks
Period Title: Overall Study
STARTED	3	2
COMPLETED	3	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Venlafaxine	Sugar Pill	Total
Arm/Group Description	225 mg daily over 12 weeks Venlafaxine: 225 mg daily for 12 weeks	Placebo: Capsule matching active drug to be taken once a day for 12 weeks	Total of all reporting groups
Overall Participants	3	2	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	1 50%	1 20%
>=65 years	3 100%	1 50%	4 80%
Sex: Female, Male (Count of Participants)
Female	2 66.7%	0 0%	2 40%
Male	1 33.3%	2 100%	3 60%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 33.3%	0 0%	1 20%
White	2 66.7%	2 100%	4 80%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Changes in Dose Response Using the Modified Alzheimer's Disease (AD) Cooperative Study-Clinical Global Impression of Change.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine	Sugar Pill
Arm/Group Description	225 mg daily over 12 weeks Venlafaxine: 225 mg daily for 12 weeks	Placebo: Capsule matching active drug to be taken once a day for 12 weeks
Measure Participants	3	2
Marked improvement according to CGI	2 66.7%	0 0%
Moderate improvement according to CGI	1 33.3%	2 100%

Adverse Events

Arm/Group Title	Venlafaxine		Sugar Pill
Arm/Group Description	225 mg daily over 12 weeks Venlafaxine: 225 mg daily for 12 weeks		Placebo: Capsule matching active drug to be taken once a day for 12 weeks
All Cause Mortality
	Venlafaxine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Serious Adverse Events
	Venlafaxine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/2 (0%)
Cardiac disorders
Hypokalemia	1/3 (33.3%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Venlafaxine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		1/2 (50%)
Cardiac disorders
Low potassium	1/3 (33.3%)	1	0/2 (0%)	0
Gastrointestinal disorders
Diarrhea	0/3 (0%)	0	1/2 (50%)	1
Nausea	1/3 (33.3%)	1	0/2 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.