DIADS-2: Depression in Alzheimer's Disease-2

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00086138
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 131
• Locations: 5
• Arms: 2
• Duration (Months): 60
• Patients Per Site: 26.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to learn whether treating individuals with Alzheimer's disease and depression with the anti-depressant medication sertraline (Zoloft) is helpful to people with Alzheimer's disease and to their families and caregivers.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease; Depression	Drug: Sertraline (Zoloft); Drug: Placebo	Phase 2/Phase 3

Detailed Description

Participants are randomly assigned to treatment with sertraline (range 25-125 mg per day) or identical placebo for 24 weeks. There are 8 scheduled in-person visits in the 24 weeks. Visits include neuropsychological testing. Caregivers are asked to are the patient on a Daily Affect Diary for 6 weeks during the study period. Telephone followup is done at weeks 36 and 48. Both groups receive caregiver support/education.

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Depression in Alzheimer's Disease (DIADS-2)
• Study Start Date: Jul 1, 2004
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Participants will receive sertraline at a target dose of 100mg daily.	Drug: Sertraline (Zoloft); Sertraline: range of 25 to 125 mg per day for 24 weeks
Placebo Comparator: 2 Participants will receive placebo matched to sertraline	Drug: Placebo; Placebo designed to mimic sertraline taken daily for 24 weeks

Outcome Measures

Primary Outcome Measures

1. Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) [Measured at Week 12]

   At each study visit, based on patient examination and caregiver interview, clinicians rated overall impression of clinical change from baseline using the modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change index (mADCS-CGIC), which in addition to the original scale incorporates a global rating of mood and associated symptoms of depression. The mADCS-CGIC uses a seven-point Likert scale, with scores ranging from 1 ("much better") to 7 ("much worse"), with a score of 4 being "no change".

Secondary Outcome Measures

1. Remission According to Cornell Scale for Depression in Dementia Scale [Measured at Weeks 12]

   The Cornell Scale for Depression in Dementia (CSDD), a 19-item scale measuring the severity of depression in dementia, utilizing input from both the caregiver and the participant. CSDD scores were imputed for 2 participants for week 2, 4 participants for week 4, 7 participants for week 8, and 12 participants for week 12.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

• Ability of the participant, caregiver or surrogate to provide written informed consent.

• Dementia due to Alzheimer's disease

• Stable treatment for Alzheimer's disease

• Ability for the participant's caregiver to accompany the participant to study visits and participate in the study.

Exclusion

• Presence of a brain disease that might otherwise explain the presence of dementia

• Clinically significant hallucinations or delusions

• Current treatment of antipsychotics, anticonvulsants, and other antidepressants, benzodiazepines, or other psychotropic medications

• Need for hospitalization or residence in a nursing facility

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033
2	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
3	University of Rochester	Rochester	New York	United States	14620
4	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
5	Medical University of South Carolina	North Charleston	South Carolina	United States	29406

Sponsors and Collaborators

• Johns Hopkins University
• National Institute of Mental Health (NIMH)

Investigators

• Study Chair: Constantine G. Lyketsos, MD, MHS, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Constantine G. Lyketsos, Chairman, Bayview Psychiatry, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00086138
• Other Study ID Numbers: U01MH066136; U01MH066136; DATR A4-GPX
• First Posted: Jun 28, 2004
• Last Update Posted: Apr 11, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Constantine G. Lyketsos, Chairman, Bayview Psychiatry, Johns Hopkins University: Alzheimer's disease; Depression
• Additional relevant MeSH terms: Alzheimer Disease; Depression; Depressive Disorder; Sertraline

Study Results

Participant Flow

Recruitment Details	Participants were recruited from memory clinics at five academic centers in the United States.

Arm/Group Title	Placebo	Sertraline
Arm/Group Description	Participants will receive placebo matched to sertraline Placebo: Placebo designed to mimic sertraline taken daily for 24 weeks	Participants will receive sertraline at a target dose of 100mg daily. Sertraline (Zoloft): Sertraline: range of 25 to 125 mg per day for 24 weeks
Period Title: Overall Study
STARTED	64	67
COMPLETED	60	64
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Sertraline	Placebo	Total
Arm/Group Description	Participants will receive sertraline at a target dose of 100mg daily. Sertraline (Zoloft): Sertraline: range of 25 to 125 mg per day for 24 weeks	Participants will receive placebo matched to sertraline Placebo: Placebo designed to mimic sertraline taken daily for 24 weeks	Total of all reporting groups
Overall Participants	67	64	131
Age, Customized (years) [Mean (Standard Deviation) ]
Age	76.5 (8)	78.2 (8)	77.3 (8)
Sex/Gender, Customized (participants) [Number]
Female	40 59.7%	31 48.4%	71 54.2%
Male	27 40.3%	33 51.6%	60 45.8%

Outcome Measures

1. Primary Outcome

Title	Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC)
Description	At each study visit, based on patient examination and caregiver interview, clinicians rated overall impression of clinical change from baseline using the modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change index (mADCS-CGIC), which in addition to the original scale incorporates a global rating of mood and associated symptoms of depression. The mADCS-CGIC uses a seven-point Likert scale, with scores ranging from 1 ("much better") to 7 ("much worse"), with a score of 4 being "no change".
Time Frame	Measured at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sertraline	Placebo
Arm/Group Description	Participants will receive sertraline at a target dose of 100mg daily. Sertraline (Zoloft): Sertraline: range of 25 to 125 mg per day for 24 weeks	Participants will receive placebo matched to sertraline Placebo: Placebo designed to mimic sertraline taken daily for 24 weeks
Measure Participants	67	64
"much worse"	1 1.5%	0 0%
"worse"	5 7.5%	2 3.1%
"a bit worse"	6 9%	9 14.1%
"no change"	10 14.9%	11 17.2%
"a bit better"	18 26.9%	18 28.1%
"better"	18 26.9%	21 32.8%
"much better"	9 13.4%	3 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sertraline, Placebo
	Comments	The statistical analyses compared data collected from the CGIC of participants who received sertraline who had a score equal to or better than the CGIC of participants who received the placebo intervention.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Remission According to Cornell Scale for Depression in Dementia Scale
Description	The Cornell Scale for Depression in Dementia (CSDD), a 19-item scale measuring the severity of depression in dementia, utilizing input from both the caregiver and the participant. CSDD scores were imputed for 2 participants for week 2, 4 participants for week 4, 7 participants for week 8, and 12 participants for week 12.
Time Frame	Measured at Weeks 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sertraline	Placebo
Arm/Group Description	Participants will receive sertraline at a target dose of 100mg daily. Sertraline (Zoloft): Sertraline: range of 25 to 125 mg per day for 24 weeks	Participants will receive placebo matched to sertraline Placebo: Placebo designed to mimic sertraline taken daily for 24 weeks
Measure Participants	67	64
Number [percentage of participants]	33 49.3%	19 29.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sertraline, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.06
	Confidence Interval	(2-Sided) 95%; 0.84 to 5.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Sertraline		Placebo
Arm/Group Description	Participants will receive sertraline at a target dose of 100mg daily. Sertraline (Zoloft): Sertraline: range of 25 to 125 mg per day for 24 weeks		Participants will receive placebo matched to sertraline Placebo: Placebo designed to mimic sertraline taken daily for 24 weeks
All Cause Mortality
	Sertraline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sertraline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/67 (19.4%)		7/64 (10.9%)
Cardiac disorders
Cardiac	3/67 (4.5%)		5/64 (7.8%)
Musculoskeletal and connective tissue disorders
Musculoskeletal	3/67 (4.5%)		1/64 (1.6%)
Nervous system disorders
Neurologic	4/67 (6%)		3/64 (4.7%)
Respiratory, thoracic and mediastinal disorders
Pneumonia/respiratory infection	4/67 (6%)		0/64 (0%)
Other (Not Including Serious) Adverse Events
	Sertraline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/67 (65.7%)		26/64 (40.6%)
Gastrointestinal disorders
Diarrhea	36/67 (53.7%)		22/64 (34.4%)
Nervous system disorders
Dizziness	44/67 (65.7%)		26/64 (40.6%)
Respiratory, thoracic and mediastinal disorders
Dry mouth	37/67 (55.2%)		23/64 (35.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.