Treatment Resistant Geriatric Depression in Primary Care
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|ClinicalTrials.gov Identifier: NCT01392287|
Recruitment Status : Completed
First Posted : July 12, 2011
Last Update Posted : February 1, 2017
|First Submitted Date ICMJE||July 11, 2011|
|First Posted Date ICMJE||July 12, 2011|
|Last Update Posted Date||February 1, 2017|
|Actual Study Start Date ICMJE||May 2010|
|Actual Primary Completion Date||April 2012 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Mean Differences in NAAG Levels between Subject Groups at Baseline and Week 8 [ Time Frame: Baseline / Study Entry ]
Are NAAG levels are lower in older adults with treatment resistant depression compared with healthy age-matched controls?
|Original Primary Outcome Measures ICMJE
||To determine if NAAG levels are lower in older adults with treatment resistant depression compared with healthy age-matched controls. [ Time Frame: Baseline / Study Entry ]
Comparing baseline NAAG levels in older adults with treatment resistant depression and age-matched controls using 3T MRI spectroscopy.
|Change History||Complete list of historical versions of study NCT01392287 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Treatment Resistant Geriatric Depression in Primary Care|
|Official Title ICMJE||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?|
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:
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:
RESEARCH DESIGN AND METHODS
We will enroll up to 20 subjects with major depression, ages 55-89, and up to 20 healthy control subjects, ages 55-89 matched with depression group for age, sex, and ethnicity. We require 10 subjects in each group to have completed the study protocol with clinical and MRI scan data suitable for analysis.
Subjects in both groups will be recruited from:
One site (McLean Hospital) is engaged in this protocol. CHA and other sites only refer subjects to McLean and do not consent subjects or complete any study protocol procedures. Subjects must meet all selection criteria in order to participate in the study protocol.
All subjects will complete a brief pre-screening interview over the phone or in person in order to assess their preliminary eligibility for study inclusion.
After signing consent, all study subjects will follow the same screening period (with the exceptions for control subjects mentioned below). Screening procedures include a clinical diagnostic interview, medical monitoring, physical exam, collecting information regarding prior and concomitant medication and adverse events, blood draw, vital signs, height, and weight, demographic and clinical history information, as well as assessments of daily functioning, mood, anxiety, and cognition.
Visit 2 / Baseline (Week 0):
Depression subjects will return to the office after the completion of screening procedures (within 14 days of signing consent) to complete baseline procedures which include assessments of daily functioning, fatigue, mood, anxiety, medical monitoring, psychiatric interview, concomitant medications, adverse events, vitals, 3T scan, EEG with resting state and Flanker Task procedures (prior to receiving study medication), spirituality questionnaire, and urine pregnancy test (if applicable). Neuropsychological tests will also be completed at this visit.
No changes in psychotropic drugs will be allowed for depression subjects during this the screening period before study drug is administered. The subjects with depression will be administered (before leaving the office) memantine HCl 5 mg tablets. All depression subjects will start at a dose of 5 mg once per day in the morning.
Visit 3 (Week 1) and Visit 4 (Week 2):
Following the completion of Visit 2, the subject will return to the office for 2 visits in 2 consecutive weeks. A psychiatric interview, review concomitant medications and AEs (if any), mood and anxiety scales, monitoring of medication tolerability and compliance, vital sign collection will be completed at these visits. Study medication will be dispensed and depression subjects will be instructed according to the dosing schedule.
Visit 5 (Week 4) and 6 (Week 6):
After completing Visit 4, subjects will return to the office 2 weeks later for Visit 5 (Week 4) and then 2 weeks after that for Visit 6 (Week 6). The same visit procedures will be completed at these visits as Visits 3 and 4, except the subject will not meet with the study psychiatrist at Visit 6 (Week 6). Subjects may complete Visit 6 in person or over the phone.
Visit 7 (Week 8) Final Study Visit:
After completing 8 weeks on study medication, the subject will return to the office for the final study visit. This visit will complete the same procedures as Visits 3 through 6 with the addition of another 3T scan (with a negative urine pregnancy test, if applicable), EEG (with resting state and Flanker Task) and neuropsychological tests. Participants will also repeat spirituality and fatigue questionnaires with assistance from study staff.
Subjects will be asked to return all study medication for the final visit. At this time subjects will have the option of staying on the medication or tapering off study medication and being referred to the McLean Hospital Geriatric Outpatient Clinic for follow up or to an appropriate physician of their choice. We will share information regarding study participation and results with the subjects' primary care physician and/or other entities only if the subject has completed an "Authorization for Release of Medical Records" form. If the subjects chose to discontinue treatment with memantine HCl, the psychiatrist (BPF) will instruct subjects how to safely taper off study medication.
Control Subject Visits:
Following screening, control subjects will return to the office for 3 visits. Unlike the depression group, the control group will NOT receive the study drug memantine HCl. Control subjects are not scheduled to meet with the study psychiatrist at the Baseline Week 0 and Week 8 visits and complete blood draw and one of the neuropsychological tests during participation. Other than the exceptions previously mentioned, control subjects will follow the same protocol as the depression subjects for the screening period, Baseline (Week 0), and Week 8 Visit. Study staff will monitor adverse events (if any occur), use of concomitant medication (if any), and subject safety throughout study participation. Vital signs will also be collected at every visit. Mood measures, spirituality and fatigue questionnaires, and neuropsychological tests identical to those administered to the depression group will be completed during the Week 8 final visit. Controls will also complete the same 3T MRI scanning protocol as depression subjects. Controls also have the opportunity to participate in EEG acquisition at baseline and study endpoint.
We plan to contact enrolled subjects after the last subject completes the study per protocol and the data has been analyzed. This follow-up correspondence will consist of at least 3 attempts to contact subjects' by phone and 1 certified letter sharing our research findings with subjects.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
|Condition ICMJE||Major Depressive Disorder|
|Intervention ICMJE||Drug: Memantine
Dosing Form: Tablet
Dosage: 5mg, 10 mg
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)
|Study Arms||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.
Intervention: Drug: Memantine
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date||April 2012|
|Actual Primary Completion Date||April 2012 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Inclusion Criteria for Depression Subjects:
Exclusion Criteria for Depression Subjects:
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:
Exclusion Criteria for Control Subjects:
|Ages||55 Years to 89 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01392287|
|Other Study ID Numbers ICMJE||2010-P-001094|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||
|Responsible Party||Brent Forester, Mclean Hospital|
|Study Sponsor ICMJE||Mclean Hospital|
|PRS Account||Mclean Hospital|
|Verification Date||January 2017|
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