Treatment Resistant Geriatric Depression in Primary Care

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2012 by Mclean Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Cambridge Health Alliance
Harvard University
Information provided by (Responsible Party):
Brent Forester, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01392287
First received: July 11, 2011
Last updated: August 28, 2013
Last verified: May 2012
  Purpose

This study involves collaboration between McLean Hospital, Geriatric Medicine at the Cambridge Health Alliance (CHA) and other sites within the Partners and Harvard Medical School network. The investigators plan to recruit individuals 55 to 89 years old with treatment resistant depression. Someone with "treatment resistant" depression for this study may be someone who still has sad or low feelings and thoughts even though he/she is taking an antidepressant medication for at least 8 weeks to help relieve his/her depression. During the study, subjects will gradually add memantine hydrochloride in dosages up to 20 mg/day for 8 weeks to their standard antidepressant treatment.

The investigators are doing this research study to help answer 3 questions:

  1. Do older adults with treatment resistant Major Depression have lower levels of a chemical in the brain called NAAG than older adults without Major Depression?
  2. Do older adults with naturally low NAAG levels do better on memantine hydrochloride treatment than older adults with higher amounts of this chemical on memantine hydrochloride treatment?
  3. Do older adults with treatment resistant depression have more problems with memory and concentration than older adults without depression?

The investigators are also interested in looking at electrical and neuronal activity of the brain, spiritual beliefs, and fatigue in relationship to depression.

The investigators hypothesize that:

  1. Older individuals with treatment resistant Major Depression will have lower levels of NAAG compared with age-matched older control subjects.
  2. Older adults with treatment resistant depression and low NAAG levels will do better on treatment with memantine hydrochloride than older adults on memantine with higher NAAG levels.
  3. Older adults with depression will do better on tests of attention and executive functioning after treatment with memantine hydrochloride.
  4. Healthy controls will do better on tests of attention and executive functioning than older adults with depression.

Condition Intervention Phase
Major Depressive Disorder
Drug: Memantine
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Treatment Resistant Geriatric Depression in Primary Care: Is NAAG (N-Acetylaspartylglutamate), Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) at 3 Tesla, a Predictor of Treatment Response?

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Mean Differences in NAAG Levels between Subject Groups at Baseline and Week 8 [ Time Frame: Baseline / Study Entry ] [ Designated as safety issue: No ]
    Are NAAG levels are lower in older adults with treatment resistant depression compared with healthy age-matched controls?


Secondary Outcome Measures:
  • Relationship of NAAG Levels and MADRS Scores between Subject Groups at Baseline and Week 8 [ Time Frame: 8-week trial ] [ Designated as safety issue: No ]
    Do subjects with low NAAG levels within the treatment resistant depression group prior to memantine hydrochloride augmentation respond better to treatment with memantine hydrochloride?

  • Cognitive Impairment between Subject Groups at Baseline and Week 8 [ Time Frame: 8-week trial ] [ Designated as safety issue: No ]
    Do older adults with Major Depression have evidence of cognitive impairment (in particular in the realm of executive functioning and attention) compared with older healthy controls from baseline to study endpoint?


Enrollment: 12
Study Start Date: August 2010
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Memantine hydrochloride
Older individuals with DSM IV TR Major Depression, with persistent symptoms of depression despite at least 8 weeks of treatment with standard pharmacotherapy, will be referred for a study of memantine hydrochloride augmentation. Healthy control subjects follow similar study schedule for baseline and endpoint but do not receive memantine hydrochloride.
Drug: Memantine

Dosing Form: Tablet

Dosage: 5mg, 10 mg

Description:

Memantine hydrochloride (Namenda®), a low to moderate affinity uncompetitive (open-channel) NMDA antagonist, is manufactured and supplied by Forest Laboratories, Incorporated. Only the subjects in the depression group will receive the study drug memantine HCl. Per psychiatrist's instructions, subjects may remain on the maximum dosage of memantine HCl allowed by the study protocol for a given week, or reduce the dosage if concerns regarding tolerability arise. The dosage of memantine HCl cannot be increased more rapidly than the dosing schedule listed below.

Memantine HCl Dosing Schedule:

5 mg qAM week 1 5 mg qAM and 5 mg qHS for week 2 10 mg qAM and 5 mg qHS for week 3 10 mg BID for week 4, 5, 6, 7, and 8

Other Name: Namenda (NDA # 021487)

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  Eligibility

Ages Eligible for Study:   55 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for Depression Subjects:

  • Ability to provide informed consent
  • Age 55 to 89, inclusive
  • DSM-IV Diagnosis of Major Depressive Disorder
  • MADRS score of >16 at screening and baseline*
  • Must speak, read, and write in English
  • On standard antidepressant medication for at least 8 weeks prior to beginning memantine hydrochloride treatment

Exclusion Criteria for Depression Subjects:

  • Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
  • History of seizure disorder
  • History or current diagnosis of the following psychiatric illnesses: any organic mental disorder (including dementia), schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, bipolar disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months
  • History of drug hypersensitivity or intolerance to memantine hydrochloride
  • Use of the following class of medications: barbiturates.**
  • Inability to complete the screening procedures
  • Contraindications to magnetic resonance imagining (MRI), including any of the exclusion criteria mentioned in the MRI risks section of this protocol
  • MRI abnormality that compromises integrity of imaging data (eg. intracranial lesions, hydrocephalus)
  • Non-English speaking participants

Notes for Study Criteria (Depressed Subjects):

*Depressed subjects that score below a 16 on the MADRS at baseline may be reevaluated within two weeks. After reevaluation, study staff will exclude subjects that continue to score below a 16 on the MADRS. All subjects who score 16 or above at reevaluation may be included in the study at that point, provided they still meet study criteria.

**Benzodiazepines and non-benzodiazepine sedative hypnotics (such as zolpidem/Ambien), may be used by depressed subjects throughout the study as long as they are not taken within 12 hours of any MRI scan.

Inclusion Criteria for Control Subjects:

  • Ability to provide informed consent
  • Age 55 to 89, inclusive
  • MADRS score <4
  • Must speak, read, and write in English
  • Must match with a depression subject previously enrolled on age (+/- 5 years) and sex

Exclusion Criteria for Control Subjects:

  • Any evidence of current or past psychiatric disorders
  • Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
  • History of seizure disorder
  • History or current diagnosis of the following psychiatric illnesses: any organic mental disorder (including dementia), major depressive disorder, depression NOS, dysthymia, bipolar disorder( type I or II), schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, bipolar major depressive disorder, patients with substance dependence disorders, including alcohol.
  • Use of any class of psychotropic medication.
  • Inability to complete the screening visit
  • MRI abnormality that compromises integrity of imaging data
  • Contraindications to magnetic resonance imagining (MRI), including any of the exclusion criteria mentioned in the MRI risks section of this protocol
  • Non-English speaking participants
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01392287

Locations
United States, Massachusetts
McLean Hospital
Belmont, Massachusetts, United States, 02478
Sponsors and Collaborators
Mclean Hospital
Cambridge Health Alliance
Harvard University
Investigators
Principal Investigator: Brent P Forester, M.D. Mclean Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Brent Forester, Geriatric Psychiatrist / Principal Investigator, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01392287     History of Changes
Other Study ID Numbers: 2010-P-001094
Study First Received: July 11, 2011
Last Updated: August 28, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Mclean Hospital:
Geriatric
Older adults
Major Depressive Disorder
Magnetic Resonance Spectroscopy
memantine hydrochloride
N-Acetylaspartylglutamate
NAAG
Cognitive impairment

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Memantine
N-acetyl-1-aspartylglutamic acid
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neuroprotective Agents
Protective Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on August 20, 2014