Memantine Treatment for Improving Rehabilitation Outcomes and Preventing Depression in Older Adults

• Sponsor: Eric Lenze (Other)
• Overall Status: Completed
• CT.gov ID: NCT00183729
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 35
• Location: 1
• Arms: 2
• Duration (Months): 46
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This study will evaluate the effectiveness of memantine in improving rehabilitation outcomes and preventing major depressive disorder in older adults who have been admitted to a rehabilitation hospital for a hip fracture or cardiopulmonary condition.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: Memantine; Other: Placebo	Phase 4

Detailed Description

Depression is a serious medical illness that is often difficult to diagnose and treat. It occurs in people of all ages, but is often overlooked in older adults. Depression frequently co-occurs with other serious illnesses, and may be mistaken by both patients and health care givers as a normal consequence of the illness. However, these misconceptions toward depression contribute to the underdiagnosis and undertreatment of depressive disorders in older people. In turn, depression may hinder a patient's recovery from an illness. This study will evaluate the effectiveness of memantine in improving rehabilitation outcomes and preventing major depressive disorder in older adults who have been admitted to a rehabilitation hospital for a hip fracture or a cardiopulmonary condition.

This double-blind study will last for 12 months. Participants will be randomly assigned to receive either placebo or memantine, which is a drug that is often used to treat Alzheimer's disease. Both memantine and placebo will be administered to participants for 12 weeks. All participants will be followed for an additional 40 weeks. Outcome measurements will include participants' depressive symptoms, motivation, and learned helplessness. In addition, medication side effects, functional outcome, and incidence of major depressive disorder will be measured. All measurements will be taken at Week 12 and Month 12.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Memantine for Enhancement of Rehabilitation Efficacy and Prevention of Major Depressive Disorder in Older Adults
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Memantine (1) Memantine for 12 weeks	Drug: Memantine; Memantine dosage is started at 10 mg daily and is increased at Week 1 as tolerated to 10 mg two times a day.; Other Names: Namenda
Placebo Comparator: Placebo (2) Placebo for 12 weeks	Other: Placebo; Placebo distribution is planned to mimic the active drug.

Outcome Measures

Primary Outcome Measures

1. Depressive Symptoms [week 0, week 12]

   Hamilton depression rating scale ; scale ranges 0 (no symptoms) to 52 (severe depression)

Secondary Outcome Measures

1. Incidence of Major Depressive Disorder [week 12]

   cumulative incidence over 12 weeks of follow-up

2. Functional Recovery [week 0, week 12]

   Functional Independence Msure, 13-item motor subscale (scale ranges 13-91, higher scores = better function)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Admission to a skilled nursing facility for rehabilitation within 3 months of recent disabling medical event (e.g., hip fracture)

• Medically stable (e.g., no active seizures, delirium, unstable pulse/blood pressure)

Exclusion Criteria:

• Aphasia or cognitive impairments sufficiently severe to prevent valid assessment (e.g., a score of less than 22 on the Mini Mental State Examination)

• Current major depressive episode

• History of or current psychosis or mania

• Current substance or alcohol abuse or dependence (within 3 months of study entry)

• Current use of memantine

• Sensitivity or contraindication to memantine

• End-stage kidney, liver, heart, or lung disease

• Recent hemorrhagic stroke

• A FIM score of greater than 70 (on a 91 point scale)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Eric Lenze
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Eric J. Lenze, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eric Lenze, Professor of Psychiatry, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00183729
• Other Study ID Numbers: K23MH064196-02; K23MH064196-02
• First Posted: Sep 16, 2005
• Last Update Posted: Jan 17, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eric Lenze, Professor of Psychiatry, University of Pittsburgh: Major depressive disorder; Rehabilitating; Elderly; Apathy
• Additional relevant MeSH terms: Depression; Depressive Disorder; Memantine

Study Results

Participant Flow

Recruitment Details	35 subjects were randomized
Pre-assignment Detail	No significant events. Please see Lenze et al, Int J of Geriatric Psychiatry 2012 article for details.

Arm/Group Title	Memantine (1)	Placebo (2)
Arm/Group Description	Memantine for 12 weeks Memantine: Memantine dosage is started at 10 mg daily and is increased at Week 1 as tolerated to 10 mg two times a day.	Placebo for 12 weeks Placebo: Placebo distribution is planned to mimic the active drug.
Period Title: Overall Study
STARTED	17	18
COMPLETED	14	13
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Memantine (1)	Placebo (2)	Total
Arm/Group Description	Memantine for 12 weeks Memantine: Memantine dosage is started at 10 mg daily and is increased at Week 1 as tolerated to 10 mg two times a day.	Placebo for 12 weeks Placebo: Placebo distribution is planned to mimic the active drug.	Total of all reporting groups
Overall Participants	17	18	35
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	17 100%	18 100%	35 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	80.1 (9.7)	78 (9.2)	79.1 (9.5)
Sex: Female, Male (Count of Participants)
Female	14 82.4%	14 77.8%	28 80%
Male	3 17.6%	4 22.2%	7 20%
Region of Enrollment (participants) [Number]
United States	17 100%	18 100%	35 100%

Outcome Measures

1. Primary Outcome

Title	Depressive Symptoms
Description	Hamilton depression rating scale ; scale ranges 0 (no symptoms) to 52 (severe depression)
Time Frame	week 0, week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Memantine (1)	Placebo (2)
Arm/Group Description	Memantine for 12 weeks Memantine: Memantine dosage is started at 10 mg daily and is increased at Week 1 as tolerated to 10 mg two times a day.	Placebo for 12 weeks Placebo: Placebo distribution is planned to mimic the active drug.
Measure Participants	17	18
Week 0	12.5 (3.6)	13.4 (3.7)
Week 12	7 (1.5)	5.2 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Memantine (1), Placebo (2)
	Comments	Null: the two groups would not differ in depressive symptoms over time (ie both groups would improve equally in terms of their depressive symptoms) Power calculation: none; this was a pilot study
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2
	Estimation Comments

2. Secondary Outcome

Title	Incidence of Major Depressive Disorder
Description	cumulative incidence over 12 weeks of follow-up
Time Frame	week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Memantine (1)	Placebo (2)
Arm/Group Description	Memantine for 12 weeks Memantine: Memantine dosage is started at 10 mg daily and is increased at Week 1 as tolerated to 10 mg two times a day.	Placebo for 12 weeks Placebo: Placebo distribution is planned to mimic the active drug.
Measure Participants	17	18
Count of Participants [Participants]	3 17.6%	1 5.6%

3. Secondary Outcome

Title	Functional Recovery
Description	Functional Independence Msure, 13-item motor subscale (scale ranges 13-91, higher scores = better function)
Time Frame	week 0, week 12

Outcome Measure Data

Analysis Population Description

intent to treat analysis; data presented are the week 12 data from the mixed effect model

Arm/Group Title	Memantine (1)	Placebo (2)
Arm/Group Description	Memantine for 12 weeks Memantine: Memantine dosage is started at 10 mg daily and is increased at Week 1 as tolerated to 10 mg two times a day.	Placebo for 12 weeks Placebo: Placebo distribution is planned to mimic the active drug.
Measure Participants	17	18
Least Squares Mean (Standard Error) [units on a scale]	73 (7)	81 (6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Memantine (1), Placebo (2)
	Comments	Null hypothesis: functional recovery would be the same in both groups. Power calculation: none. This was a pilot study.
	Type of Statistical Test	Superiority
	Comments	(no comments)
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7
	Estimation Comments

Adverse Events

Arm/Group Title	Memantine (1)		Placebo (2)
Arm/Group Description	Memantine for 12 weeks Memantine: Memantine dosage is started at 10 mg daily and is increased at Week 1 as tolerated to 10 mg two times a day.		Placebo for 12 weeks Placebo: Placebo distribution is planned to mimic the active drug.
All Cause Mortality
	Memantine (1)		Placebo (2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Memantine (1)		Placebo (2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Memantine (1)		Placebo (2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/18 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.