Effectiveness of Nimodipine Plus Antidepressant Medication in Treating Vascular Depression

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00781326
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 9
• Location: 1
• Arm: 1
• Duration (Months): 6
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This study will examine whether combined use of an antidepressant medication and the medication nimodipine reduces risk of depression relapse in patients with vascular depression.

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

Detailed Description

Depressed elderly patients often show signs of cerebrovascular disease, commonly known as a stroke. Some scientists theorize that having cerebrovascular disease may affect depression in older adults in one of three ways: by causing depression, by making it more likely that people who have been depressed have a relapse, or by maintaining certain depressive symptoms in those already depressed. The combination of depression and cerebrovascular disease in older adults is referred to as vascular depression and is associated with psychomotor slowing, functional impairment, and cognitive impairment. Additionally, the likelihood of improvement or remission is lower in vascular depression and is more difficult to treat over time.

Nimodipine (NIM) is FDA approved to reduce incidence and severity of problems with blood flow resulting from a particular type of stroke. In addition to improving blood flow in the brain following a stroke, NIM also protects neurons from injury or degeneration and has cognitive and functional benefits. These positive effects of NIM may make it useful for treatment of vascular depression. In a previous study of people with vascular depression, pairing NIM with the antidepressant fluoxetine showed greater improvements in depression treatment outcomes, higher likelihood of full remission, and less incidence of depression recurrence than using fluoxetine alone. This study will examine whether pairing NIM with other antidepressants will reduce recurrence of vascular depression.

Participation in this study will last 56 weeks and will be divided into two phases. In the first phase, participants will receive antidepressant medication without NIM. Participants will begin taking escitalopram but may be switched to duloxetine or have lorazepam added to their regimen, depending on individual treatment effectiveness and side effects. The first phase will last between 6 and 24 weeks, ending when the individual participant either responds to medication or experiences 24 weeks of nonresponse. During the first phase, participants will attend weekly study visits, during which researchers will assess medication effectiveness and monitor side effects.

At the beginning of the second phase, participants will be randomly assigned to receive either NIM or a placebo in addition to continuing with the antidepressant medication already helping them. Participants will take NIM or the placebo for 8 months, undergoing weekly study visits for the first month and monthly study visits for the last 7 months. During these visits, researchers will monitor the participants' health and reactions to their medications. After 4, 16, and 32 weeks, an EKG test will be performed, and after 16 and 32 weeks, cognitive and physical tests will be performed again. After the 8 months, participants will attend three weekly study visits while their use of medication is lowered and then ended.

For information on a related study, please follow this link:

http://clinicaltrials.gov/show/NCT00177424

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Depression Occurring in the Setting of Cerebrovascular Risk -- A Pilot Study
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Other: Open Label Antidepressant In Phase 1, all participants will be placed on antidepressant medication. In Phase 2, participants will continue with their antidepressant medication and also receive receive either nimodipine or placebo.

Drug: Nimodipine; Nimodipine will be initiated at one, 30-mg tablet three times a day for 1 week, increased to 2 tablets three times a day for 1 week, and then increased to three tablets three times a day for the remaining 30 weeks of the study. Participants who cannot tolerate the maximum dose of 270 mg/day will be maintained at the highest tolerable dose.; Other Names: Nimotop ; Drug: Placebo; Placebo will be given in doses matching those of nimodipine.

Outcome Measures

Primary Outcome Measures

1. Hamilton Depression Rating Scale (24 Item) [Phase I Primary Outcome] [End of Phase I (at 24 weeks)]

   Hamilton Depression Rating Scale (24 item) measures symptoms of major depression. We report total score which is the sum of all items. Total score range is 0 to 76 with higher scores indicating more severe depression. We reports scores at end of Phase I for subjects completing the phase.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Current DSM-IV (Diagnostic and Statistical Manual) diagnosis of major depression

• Score greater than 15 on the 24-item Hamilton Depression Rating Scale (HDRS24)

• Significant cerebrovascular disease risk factors, as defined by the presence of more than three of the following:

1. Arterial hypertension, defined by a systolic blood pressure higher than 140 mm Hg or a diastolic blood pressure higher than 90 mm Hg, or by both a self-reported hypertension diagnosis and use of antihypertensive medication

2. Diabetes mellitus, defined by a fasting blood glucose level higher than 126 mg/dl or treatment with hypoglycemic agents or insulin in the year before study entry

3. Obesity, defined by a current body mass index (BMI) greater than 30

4. Hyperlipidemia, defined by either a confirmed prior diagnosis or a current fasting cholesterol level higher than 200 mg/dl

5. Current smoker

• Able to swallow oral medication

• Identification of a family member or friend willing and able to participate as a source of corroborating information

• Able to speak English

• A hearing capacity adequate to respond to a raised conversational voice

Exclusion Criteria:

• Current diagnosis of major depression with psychosis, schizophrenia, bipolar disorder, schizophreniform disorder, schizoaffective disorder, schizotypal disorder, or obsessive compulsive disorder

• Meets DSM-IV criteria for dementia or has a score of 17 or lower on the Mini Mental State Examination

• Met DSM-IV criteria for drug or alcohol dependence within the past 6 months

• Not responsive to therapeutic trials of either escitalopram or duloxetine for the current major depressive episode

• Acute, severe, or unstable medical disorder likely to interfere with treatment, such as untreated thyroid disorder

• History of epilepsy

• Clinically reported stroke within the past year

• First-degree heart block, determined after correcting for age

• Symptomatic hypotension or symptomatic orthostatic hypotension

• History of nontolerance or allergy to both escitalopram and duloxetine therapy, including history of selective serotonin reuptake inhibitor (SSRI)-related syndrome of inappropriate anti-diuretic hormone secretion (SIADH)

• Significant allergy to NIM or other ingredients contained in the study medication

• Taken monoamine oxidase inhibitors (MAOIs) within the 2 weeks prior to the first administration of double-blind study medication

• Requires treatment with amiodarone, protease inhibitors, dalfopristin or quinupristin, valproic acid, triazole antifungal agents (e.g., itraconazole), reserpine, methyldopa, guanethidine, or clonidine during the course of the study

• May require drugs known to interact with NIM during the course of the study

• Refusal to allow the research team to contact participant's primary medical provider

• Planning to become pregnant during the course of the study

Contacts and Locations

Locations

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

Sponsors and Collaborators

• University of Pittsburgh
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Ellen M. Whyte, MD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

• Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M. 'Vascular depression' hypothesis. Arch Gen Psychiatry. 1997 Oct;54(10):915-22. Review.
• Coffey CE, Figiel GS, Djang WT, Weiner RD. Subcortical hyperintensity on magnetic resonance imaging: a comparison of normal and depressed elderly subjects. Am J Psychiatry. 1990 Feb;147(2):187-9.
• Figiel GS, Krishnan KR, Doraiswamy PM, Rao VP, Nemeroff CB, Boyko OB. Subcortical hyperintensities on brain magnetic resonance imaging: a comparison between late age onset and early onset elderly depressed subjects. Neurobiol Aging. 1991 May-Jun;12(3):245-7.
• Hickie I, Scott E, Mitchell P, Wilhelm K, Austin MP, Bennett B. Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression. Biol Psychiatry. 1995 Feb 1;37(3):151-60.
• Simpson S, Baldwin RC, Jackson A, Burns A, Thomas P. Is the clinical expression of late-life depression influenced by brain changes? MRI subcortical neuroanatomical correlates of depressive symptoms. Int Psychogeriatr. 2000 Dec;12(4):425-34.
• Simpson SW, Jackson A, Baldwin RC, Burns A. 1997 IPA/Bayer Research Awards in Psychogeriatrics. Subcortical hyperintensities in late-life depression: acute response to treatment and neuropsychological impairment. Int Psychogeriatr. 1997 Sep;9(3):257-75.
• Taragano FE, Bagnatti P, Allegri RF. A double-blind, randomized clinical trial to assess the augmentation with nimodipine of antidepressant therapy in the treatment of "vascular depression". Int Psychogeriatr. 2005 Sep;17(3):487-98.

• Responsible Party: Ellen Whyte, Assistant Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00781326
• Other Study ID Numbers: K23MH067710-01; K23MH067710-01; DATR AK-TNGP1
• First Posted: Oct 29, 2008
• Last Update Posted: Sep 29, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Ellen Whyte, Assistant Professor, University of Pittsburgh: Depressive Disorder, Major; Cerebrovascular Disorders; Risk Factors; Nimodipine
• Additional relevant MeSH terms: Depression; Depressive Disorder; Nimodipine

Study Results

Participant Flow

Arm/Group Title	Open Label Antidepressant
Arm/Group Description	In Phase 1, all participants will be placed on antidepressant medication. In Phase 2, participants will continue with their antidepressant medication and also receive receive either nimodipine or placebo.
Period Title: Phase I
STARTED	6
COMPLETED	2
NOT COMPLETED	4
Period Title: Phase I
STARTED	0
COMPLETED	0
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Open Label Antidepressant
Arm/Group Description	In Phase 1, all participants will be placed on antidepressant medication. In Phase 2, participants will continue with their antidepressant medication and also receive receive either nimodipine or placebo.
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 50%
>=65 years	3 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.2 (8.7)
Sex: Female, Male (Count of Participants)
Female	5 83.3%
Male	1 16.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 16.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 50%
White	2 33.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%
Hamilton Depression Rating Scale (24 item) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	20.5 (2.4)
Cumulative Illness Rating Scale (Geriatric) total (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	8.3 (2.0)

Outcome Measures

1. Primary Outcome

Title	Hamilton Depression Rating Scale (24 Item) [Phase I Primary Outcome]
Description	Hamilton Depression Rating Scale (24 item) measures symptoms of major depression. We report total score which is the sum of all items. Total score range is 0 to 76 with higher scores indicating more severe depression. We reports scores at end of Phase I for subjects completing the phase.
Time Frame	End of Phase I (at 24 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label Antidepressant
Arm/Group Description	In Phase 1, all participants will be placed on antidepressant medication. In Phase 2, participants will continue with their antidepressant medication and also receive receive either nimodipine or placebo. Nimodipine: Nimodipine will be initiated at one, 30-mg tablet three times a day for 1 week, increased to 2 tablets three times a day for 1 week, and then increased to three tablets three times a day for the remaining 30 weeks of the study. Participants who cannot tolerate the maximum dose of 270 mg/day will be maintained at the highest tolerable dose. Placebo: Placebo will be given in doses matching those of nimodipine.
Measure Participants	2
Mean (Standard Deviation) [units on a scale]	9.5 (0.7)

Adverse Events

Time Frame	Phase I (at or before 24 weeks)
Arm/Group Title	Open Label Antidepressant
Arm/Group Description	In Phase 1, all participants will be placed on antidepressant medication. In Phase 2, participants will continue with their antidepressant medication and also receive receive either nimodipine or placebo.
All Cause Mortality
	Open Label Antidepressant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Open Label Antidepressant
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Psychiatric disorders
Mania	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	Open Label Antidepressant
	Affected / at Risk (%)	# Events
Total	0/6 (0%)

Limitations/Caveats

Study was terminated for administrative reasons at the end of Phase I (open label antidepressant treatment). No subjects entered Phase II (Nimodipine vs Placebo).

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.