Treatment Resistant Geriatric Depression in Primary Care

NCT01392287 | Completed Phase 1

• 1 other identifier: 2010-P-001094
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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. 3.Do older adults with treatment resistant depression have more problems with memory and concentration than older adults without depression?
4. 4.Older individuals with treatment resistant Major Depression will have lower levels of NAAG compared with age-matched older control subjects.
5. 5.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.
6. 6.Older adults with depression will do better on tests of attention and executive functioning after treatment with memantine hydrochloride.
7. 7.Healthy controls will do better on tests of attention and executive functioning than older adults with depression.

Conditions

Major Depressive Disorder

Keywords

Geriatric; Older adults; Major Depressive Disorder; Magnetic Resonance Spectroscopy; memantine hydrochloride; N-Acetylaspartylglutamate; NAAG; Cognitive impairment

Outcome Measures

Primary Outcomes (1)

• Mean Differences in NAAG Levels between Subject Groups at Baseline and Week 8

  Are NAAG levels are lower in older adults with treatment resistant depression compared with healthy age-matched controls?

  Baseline / Study Entry

Secondary Outcomes (2)

• Relationship of NAAG Levels and MADRS Scores between Subject Groups at Baseline and Week 8

  8-week trial

• Cognitive Impairment between Subject Groups at Baseline and Week 8

  8-week trial

Study Arms (1)

Memantine hydrochloride

EXPERIMENTAL

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

Interventions

Memantine DRUG

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

Also known as: Namenda (NDA # 021487)

Memantine hydrochloride

Eligibility Criteria

• Age: 55 Years - 89 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.
• Ability to provide informed consent
• Age 55 to 89, inclusive
• MADRS score \<4
• Must speak, read, and write in English

Sponsors & Collaborators

• Mclean Hospital: lead
• Cambridge Health Alliance: collaborator
• Harvard University: collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Related Links

• Harvard Catalyst Website

MeSH Terms

Conditions

Depressive Disorder, Major; Cognitive Dysfunction

Interventions

Memantine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Brent P Forester, M.D.

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Geriatric Psychiatrist / Principal Investigator

Study Record Dates

• First Submitted: July 11, 2011
• First Posted: July 12, 2011
• Study Start: May 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: February 1, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)