Effectiveness of Nimodipine Plus Antidepressant Medication in Treating Vascular Depression

NCT00781326 | Terminated Phase 4 Results

• 2 other identifiers: K23MH067710-01DATR AK-TNGP1
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression

Keywords

Depressive Disorder, Major; Cerebrovascular Disorders; Risk Factors; Nimodipine

Outcome Measures

Primary Outcomes (1)

• Hamilton Depression Rating Scale (24 Item) [Phase I Primary Outcome]

  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.

  End of Phase I (at 24 weeks)

Study Arms (1)

Open Label Antidepressant

OTHER

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; Drug: Placebo

Interventions

Nimodipine DRUG

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.

Also known as: Nimotop

Open Label Antidepressant

Placebo DRUG

Placebo will be given in doses matching those of nimodipine.

Open Label Antidepressant

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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
• Obesity, defined by a current body mass index (BMI) greater than 30
• Hyperlipidemia, defined by either a confirmed prior diagnosis or a current fasting cholesterol level higher than 200 mg/dl
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (7)

• 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. doi: 10.1017/s1041610205001493.

  PMID: 16252380 BACKGROUND

• Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M. 'Vascular depression' hypothesis. Arch Gen Psychiatry. 1997 Oct;54(10):915-22. doi: 10.1001/archpsyc.1997.01830220033006.

  PMID: 9337771 BACKGROUND

• 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. doi: 10.1176/ajp.147.2.187.

  PMID: 2301657 BACKGROUND

• 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. doi: 10.1016/0197-4580(91)90104-r.

  PMID: 1876230 BACKGROUND

• 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. doi: 10.1016/0006-3223(94)00174-2.

  PMID: 7727623 BACKGROUND

• 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. doi: 10.1017/s1041610297004432.

  PMID: 9513027 BACKGROUND

• 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. doi: 10.1017/s1041610200006542.

  PMID: 11263709 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder, Major; Cerebrovascular Disorders

Interventions

Nimodipine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nicotinic Acids

Limitations and 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).

Results Point of Contact

• Title: Ellen Whyte, MD
• Organization: University of Pittsburgh

whyteem@upmc.edu

412 246 5066

Study Officials

• Ellen M. Whyte, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 27, 2008
• First Posted: October 29, 2008
• Study Start: August 1, 2008
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: September 29, 2016
• Results First Posted: September 29, 2016

Record last verified: 2016-08

Locations

US (1)