DepressionPhase 4NCT00781326
Effectiveness of Nimodipine Plus Antidepressant Medication in Treating Vascular Depression
A Phase 4 study testing Nimodipine in people with Depression, run by University of Pittsburgh at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Depression
- What is being tested?
- Nimodipine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Feb 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Treatment of Depression Occurring in the Setting of Cerebrovascular Risk -- A Pilot Study
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.
Read the 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
- Conditions
- Depression
- Being tested
- Nimodipine, Placebo
- Keywords
- Depressive Disorder, Major, Cerebrovascular Disorders, Risk Factors, Nimodipine
- Medical subject headings
- Depression, Depressive Disorder, Major, Cerebrovascular Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NimodipineDrug
Also called Nimotop
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.
PlaceboDrug
Placebo will be given in doses matching those of nimodipine.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Nimodipine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: End of Phase I (at 24 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2008 (estimated)
- Study startAug 2008
- Primary completionFeb 2009
- Study completionFeb 2009
Why it stopped: Final cost of study medication was significantly greater than initial estimate,
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Ellen Whyte, University of Pittsburgh
- Investigators
- Ellen M. Whyte, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00781326
- Sponsor's protocol ID
- K23MH067710-01
- Other IDs
- K23MH067710-01, DATR AK-TNGP1
- Status last verified
- Aug 2016
- First submitted
- 27 Oct 2008
- Last updated
- 29 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 16252380Alexopoulos 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.
PubMed 9337771Coffey 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.
PubMed 2301657Figiel 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.
PubMed 1876230Hickie 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.
PubMed 7727623Simpson 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.
PubMed 9513027Simpson 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.
PubMed 11263709
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Depression Occurring in the Setting of Cerebrovascular Risk -- A Pilot Study
- ClinicalTrials.gov ID
- NCT00781326
- Acronym / sponsor ID
- K23MH067710-01
- Conditions
- Depression
- Keywords
- Depressive Disorder, Major, Cerebrovascular Disorders, Risk Factors, Nimodipine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Final cost of study medication was significantly greater than initial estimate,
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Aug 2008
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 29 Oct 2008 (estimated)
- Results
- Posted 29 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open Label Antidepressant | Other | Drug: Nimodipine, Drug: PlaceboIn 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- Able to swallow oral medication
- Identification of a family member or friend willing and able to participate as a source of corroborating information
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NimodipineAlso: NimotopNimodipine 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. | Drug | Open Label Antidepressant |
| PlaceboPlacebo will be given in doses matching those of nimodipine. | Drug | Open Label Antidepressant |
Primary outcome
Hamilton Depression Rating Scale (24 Item) [Phase I Primary Outcome]
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16252380Taragano 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.
- Background: PubMed 9337771Alexopoulos 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.
- Background: PubMed 2301657Coffey 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.
- Background: PubMed 1876230Figiel 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.
- Background: PubMed 7727623Hickie 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.
- Background: PubMed 9513027Simpson 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.
- Background: PubMed 11263709Simpson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ellen M. Whyte, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nimodipine in people with Depression, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Depression Rating Scale (24 Item) [Phase I Primary Outcome] (time frame: End of Phase I (at 24 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00781326, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2016.