Major DepressionNCODENCT00570583
Neurocognitive Outcomes of Depression in the Elderly
An observational study of Major Depression and Dementia, run by Duke University at 1 site in United States.
Trial summary
Late-life depression (LLD) and cognitive impairment (CI) are significant public health problems among older adults, and their co-occurrence markedly increases disease burden and dementia risk. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Major Depression, Dementia
- How many people
- 795 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 1995to 31 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Primary care clinic Outpatient psychiatry clinic Inpatient psychiatry clinic Self-referral
Who may be able to join
- For depressed group:
- Age > 60 years
- Major depression, single episode or recurrent
- Ability to read and write English
- MMSE >25
- Willingness to participate in the follow-up study for at least two years.
Show all 11Show fewer
- For non-depressed group:
- Age > 60 years
- Ability to read and write English
- MMSE >25
- Willingness to participate in the follow-up study for at least two years.
Who cannot join
- Lifetime alcohol or drug dependence
- conditions associated with MRI abnormalities such hydrocephalus, benign and cancerous brain tumors, epilepsy, Parkinson's disease, Huntington's chorea, dementia, demyelinating diseases, etc.
- endocrine disorder other than diabetes mellitus)
- Any physical or intellectual disability that may affect completion of self rating instruments
- Established clinical diagnosis of dementia
- Other primary psychiatric disorders, including panic disorder, social phobia, OCD, non-affective psychosis (including schizo-affective disorder), schizophrenia, bipolar disorder
- Any metal or pacemaker in the body which precludes MRI.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Clinical Studies of Mental Illness Not Involving Treatment Development, Efficacy, or Effectiveness Trials Phenotype-genotype Predictors of Cognitive Outcomes in Geriatric Depression
Late-life depression (LLD) and cognitive impairment (CI) are significant public health problems among older adults, and their co-occurrence markedly increases disease burden and dementia risk. This highlights the importance of identifying and treating CI in LDD; however, current lack of reliable prognostic information from clinical, neuroimaging, and genetic data impedes research on targeted prevention and treatment. Two critical ways to close current knowledge gaps in predicting cognitive diagnostic outcomes of LLD involve: 1) increasing the number of diagnostic cases available to existing studies, and 2) using those studies to identify clinical, imaging, and genetic predictors that will improve future diagnosis. We intend to do both in the current proposal. We plan to study the following SPECIFIC AIMS:
Aim 1: Identify baseline clinical-behavioral predictors of cognitive diagnostic outcomes in LLD.
Read more
Working hypothesis: During acute LLD, CN will be associated with more frequent EOD and higher negative life stress than PCI and AD; PCI will be associated with EOD and higher frailty than CN and AD; AD will be associated with LOD, greater appetite loss, lower anxiety, and greater memory impairment than CN and PCI.
Aim 2: Use multimodal neuroimaging at baseline to identify patterns associated with cognitive diagnostic outcomes in individuals with LLD. Working Hypothesis: CN will be associated with greater white matter integrity compared with PCI and AD; PCI will be associated with lower white matter integrity and network abnormalities in anterior cingulate cortex compared with CN; AD will be associated with lower hippocampal volume compared with CN and PCI.
Aim 3: (exploratory): Explore interrelationships among candidate genes, cognitive diagnostic outcomes, and proposed phenotypic components relevant to LLD. Exploratory Hypotheses: 1) COMT val158met polymorphism will be associated with CN; 2) 5-HTTPRL and APOE ε2 polymorphisms will be associated with frailty; 3) genetic variation (SNPs) in TPH2 and AGTR1 will be associated with risk factors of AD: LOD, episodic memory, hippocampal volume, and appetite loss.
Read the detailed description
Central hypothesis: the 5-year likelihood of each cognitive diagnostic outcome is associated with distinct clinical, cognitive, and neural phenotypes during acute LLD, which in turn have distinct genotypic correlates.
Specifically, CN individuals will have earlier first onset of depression (EOD) relative to AD, more negative life stress during acute depression compared with AD and PCI, and greater white matter integrity; CN will also be associated with the AA genotype of the COMT val158met polymorphism, which may confer both neuroprotection and higher stress sensitivity. PCI will have more EOD relative to AD, greater frailty, and lower white matter integrity than NC. AD will be associated with later age of depression onset (LOD), greater appetite loss, lower anxiety, smaller hippocampal volume, and greater memory impairment. To test these hypotheses, we propose the following
- Conditions
- Major Depression, Dementia
- Keywords
- Depression, Cognitive impairment, Dementia, Neuroimaging, Genetics
- Medical subject headings
- Depressive Disorder, Major, Dementia, Depression, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Depressed | Older individuals with major depression | |
| Non-depressed | Older individuals without psychiatric disorder |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Depression status (measured by Montgomery Asberg Depression Rating Scale)
Measured: Minimum of once per year, up to 21 years
Change in Cognitive impairment (as measuring using cognitive tests including those found in the CERAD battery)
Measured: Once per year, up to 21 years
Development of dementia (Determined by Clinical Consensus Conference)
Measured: once per year, up to 14 years
Secondary outcomes (3)
Change in Cognition (as measured by tests including those in the CERAD battery) Change in Brain MRI markers (e.g., volume of white matter and gray matter lesions)
Measured: once per year, up to 21 years
Change in Impairment in Instrumental or Basic Activities of Daily Living
Measured: at least once per year, up to 21 years
Packing density of prefrontal cortex neurons with pyramidal morphology in post-mortem neuroanatomical studies
Measured: once post-mortem
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2007 (estimated)
- Study startDec 1995
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major DepressionStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 795 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Guy G Potter, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00570583
- Sponsor's protocol ID
- Pro00006424
- Other IDs
- 1R01MH108560-01, 0625
- Acronym
- NCODE
- Status last verified
- Aug 2020
- First submitted
- 7 Dec 2007
- Last updated
- 5 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Steffens DC, Potter GG, McQuoid DR, MacFall JR, Payne ME, Burke JR, Plassman BL, Welsh-Bohmer KA. Longitudinal magnetic resonance imaging vascular changes, apolipoprotein E genotype, and development of dementia in the neurocognitive outcomes of depression in the elderly study. Am J Geriatr Psychiatry. 2007 Oct;15(10):839-49. doi: 10.1097/JGP.0b013e318048a1a0. Epub 2007 Jul 10.
PubMed 17623814Steffens DC, Taylor WD, McQuoid DR, Krishnan KR. Short/long heterozygotes at 5HTTLPR and white matter lesions in geriatric depression. Int J Geriatr Psychiatry. 2008 Mar;23(3):244-8. doi: 10.1002/gps.1869.
PubMed 17702053Potter GG, Blackwell AD, McQuoid DR, Payne ME, Steffens DC, Sahakian BJ, Welsh-Bohmer KA, Krishnan KR. Prefrontal white matter lesions and prefrontal task impersistence in depressed and nondepressed elders. Neuropsychopharmacology. 2007 Oct;32(10):2135-42. doi: 10.1038/sj.npp.1301339. Epub 2007 Feb 14.
PubMed 17299509
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Studies of Mental Illness Not Involving Treatment Development, Efficacy, or Effectiveness Trials Phenotype-genotype Predictors of Cognitive Outcomes in Geriatric Depression
- ClinicalTrials.gov ID
- NCT00570583
- Acronym / sponsor ID
- NCODE / Pro00006424
- Conditions
- Major Depression, Dementia
- Keywords
- Depression, Cognitive impairment, Dementia, Neuroimaging, Genetics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 795 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Dec 1995
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 11 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Late-life depression (LLD) and cognitive impairment (CI) are significant public health problems among older adults, and their co-occurrence markedly increases disease burden and dementia risk. This highlights the importance of identifying and treating CI in LDD; however, current lack of reliable prognostic information from clinical, neuroimaging, and genetic data impedes research on targeted prevention and treatment. Two critical ways to close current knowledge gaps in predicting cognitive diagnostic outcomes of LLD involve: 1) increasing the number of diagnostic cases available to existing studies, and 2) using those studies to identify clinical, imaging, and genetic predictors that will improve future diagnosis. We intend to do both in the current proposal. We plan to study the following SPECIFIC AIMS:
Aim 1: Identify baseline clinical-behavioral predictors of cognitive diagnostic outcomes in LLD.
Working hypothesis: During acute LLD, CN will be associated with more frequent EOD and higher negative life stress than PCI and AD; PCI will be associated with EOD and higher frailty than CN and AD; AD will be associated with LOD, greater appetite loss, lower anxiety, and greater memory impairment than CN and PCI.
Aim 2: Use multimodal neuroimaging at baseline to identify patterns associated with cognitive diagnostic outcomes in individuals with LLD. Working Hypothesis: CN will be associated with greater white matter integrity compared with PCI and AD; PCI will be associated with lower white matter integrity and network abnormalities in anterior cingulate cortex compared with CN; AD will be associated with lower hippocampal volume compared with CN and PCI.
Aim 3: (exploratory): Explore interrelationships among candidate genes, cognitive diagnostic outcomes, and proposed phenotypic components relevant to LLD. Exploratory Hypotheses: 1) COMT val158met polymorphism will be associated with CN; 2) 5-HTTPRL and APOE ε2 polymorphisms will be associated with frailty; 3) genetic variation (SNPs) in TPH2 and AGTR1 will be associated with risk factors of AD: LOD, episodic memory, hippocampal volume, and appetite loss.
Detailed description
Central hypothesis: the 5-year likelihood of each cognitive diagnostic outcome is associated with distinct clinical, cognitive, and neural phenotypes during acute LLD, which in turn have distinct genotypic correlates.
Specifically, CN individuals will have earlier first onset of depression (EOD) relative to AD, more negative life stress during acute depression compared with AD and PCI, and greater white matter integrity; CN will also be associated with the AA genotype of the COMT val158met polymorphism, which may confer both neuroprotection and higher stress sensitivity. PCI will have more EOD relative to AD, greater frailty, and lower white matter integrity than NC. AD will be associated with later age of depression onset (LOD), greater appetite loss, lower anxiety, smaller hippocampal volume, and greater memory impairment. To test these hypotheses, we propose the following
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Depressed | – | –Older individuals with major depression |
| Non-depressed | – | –Older individuals without psychiatric disorder |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Primary care clinic Outpatient psychiatry clinic Inpatient psychiatry clinic Self-referral
Key inclusion criteria (11 listed)
- Age > 60 years
- Major depression, single episode or recurrent
- Ability to read and write English
- MMSE >25
- Willingness to participate in the follow-up study for at least two years.
Key exclusion criteria (7 listed)
- Lifetime alcohol or drug dependence
- conditions associated with MRI abnormalities such hydrocephalus, benign and cancerous brain tumors, epilepsy, Parkinson's disease, Huntington's chorea, dementia, demyelinating diseases, etc.
- endocrine disorder other than diabetes mellitus)
- Any physical or intellectual disability that may affect completion of self rating instruments
- Established clinical diagnosis of dementia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in Depression status (measured by Montgomery Asberg Depression Rating Scale)
Time frame: Minimum of once per year, up to 21 years
Change in Cognitive impairment (as measuring using cognitive tests including those found in the CERAD battery)
Time frame: Once per year, up to 21 years
Development of dementia (Determined by Clinical Consensus Conference)
Time frame: once per year, up to 14 years
3 secondary outcomes
Change in Cognition (as measured by tests including those in the CERAD battery) Change in Brain MRI markers (e.g., volume of white matter and gray matter lesions)
Time frame: once per year, up to 21 years
Change in Impairment in Instrumental or Basic Activities of Daily Living
Time frame: at least once per year, up to 21 years
Packing density of prefrontal cortex neurons with pyramidal morphology in post-mortem neuroanatomical studies
Time frame: once post-mortem
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2020.
- Results publication: PubMed 17623814Steffens DC, Potter GG, McQuoid DR, MacFall JR, Payne ME, Burke JR, Plassman BL, Welsh-Bohmer KA. Longitudinal magnetic resonance imaging vascular changes, apolipoprotein E genotype, and development of dementia in the neurocognitive outcomes of depression in the elderly study. Am J Geriatr Psychiatry. 2007 Oct;15(10):839-49. doi: 10.1097/JGP.0b013e318048a1a0. Epub 2007 Jul 10.
- Results publication: PubMed 17702053Steffens DC, Taylor WD, McQuoid DR, Krishnan KR. Short/long heterozygotes at 5HTTLPR and white matter lesions in geriatric depression. Int J Geriatr Psychiatry. 2008 Mar;23(3):244-8. doi: 10.1002/gps.1869.
- Results publication: PubMed 17299509Potter GG, Blackwell AD, McQuoid DR, Payne ME, Steffens DC, Sahakian BJ, Welsh-Bohmer KA, Krishnan KR. Prefrontal white matter lesions and prefrontal task impersistence in depressed and nondepressed elders. Neuropsychopharmacology. 2007 Oct;32(10):2135-42. doi: 10.1038/sj.npp.1301339. Epub 2007 Feb 14.
- Longitudinal Geriatric Depression StudyLink provided by the sponsor.
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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.
Guy G Potter, PhD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depression and Dementia, run by Duke University 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 11 inclusion and 7 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: finished, as of the sponsor's last update on 5 Aug 2020. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Depression status (measured by Montgomery Asberg Depression Rating Scale) (time frame: Minimum of once per year, up to 21 years). The study lists 3 primary outcomes in all. 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 NCT00570583, which also lists 3 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 5 Aug 2020.