Frontotemporal DementiaPhase 4NCT00376051
Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia
A Phase 4 study testing Citalopram in people with Frontotemporal Dementia, run by Sunnybrook Health Sciences Centre at 2 sites in Canada.
Trial summary
Frontotemporal lobar degeneration(FTLD) is a common cause of early-onset dementia. FTLD is characterized multiple behavioral symptoms including mental rigidity, irritability, emotional blunting, disinhibition, apathy, and aggression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Frontotemporal Dementia
- What is being tested?
- Citalopram
- How many people
- 22 participants
- Where
- 2 sitesCanada
- Study dates
- Sep 2006to Sep 2009
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meet the DSM-IV criteria for primary degenerative dementia
- Meet standard clinical criteria for frontotemporal dementia (ie., frontotemporal degeneration including both the frontal/behavioural variant and primary progressive aphasia)
- Have significant behavioural problems as demonstrated by a score of at least eight on the Neuropsychiatric Inventory (NPI) an
- An independent clinical decision to receive psychotropic medication for behavioural disorders
Who cannot join
- An abnormal biochemical screening (blood cell count, vitamin B12 or thyroid function tests)
- Significant medical illness or other medical/neurological conditions which diminish cognitive function (including: drug overdose, severely disturbed liver, kidney, lung or heart function, anemia, hypothyroidism, vitamin B12 or folic acid deficiency, syphilis, uncontrolled diabetes, Parkinson's disease, Huntington's chorea, progressive supranuclear paralysis, brain tumour, subdural hematoma, multiple sclerosis, or brain trauma);
- An Hachinski ischemic score ≥444;
- Electrocardiographic, laboratory or physical evidence of significant cardiovascular disease;
- Hypertension >160 mmHg systolic or >100 mmHg diastolic;
- A brain computed tomographic scan that could not be interpreted as consistent with FTLD;
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- Presence of premorbid or current psychiatric diagnosis (including: major depression, schizophrenia, psychotic symptoms of a severity likely to provoke violent or dangerous behaviour such as command hallucinations to harm people or persecutory delusions that provoke violent reactions, psychoactive substance abuse or dependence);
- Contraindications to receiving citalopram (such as concomitant MAOI or within 2 weeks, or hypersensitivity to citalopram); or
- Ongoing need for psychotropic medications (i.e., unsuitable for washout) or administration of a depot antipsychotic injection within one treatment cycle of visit 1
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
The Baycrest Centre for Geriatric Care
Toronto, Ontario, M6A 2E1
About this study
Frontotemporal lobar degeneration(FTLD) is a common cause of early-onset dementia. FTLD is characterized multiple behavioral symptoms including mental rigidity, irritability, emotional blunting, disinhibition, apathy, and aggression. These behavioural disturbances are particularly important because they increase caregiver burden and may lead to earlier institutionalization. While the causes of FTLD are largely unknown, there is a great deal of evidence suggesting that a brain chemical called serotonin regulates many of the behaviours that are disturbed in FTLD. Our objective is therefore to determine whether dysfunction in the brain's serotonin system is responsible for behavioural problems among FTLD patients. We hope to take the first steps towards a scientific understanding of the behavioural symptoms of FTD, and use our findings to support a larger study optimizing the treatment of targeted behavioural disturbances in FTLD using the antidepressant citalopram.
Citalopram increases transmission by serotonin; we plan to use this medication to determine whether there are any differences in how the serotonin system functions in FTLD patients who display different levels of behavioural disturbances. Patients will be given citalopram and will have their blood drawn after 2 and 3 hours to determine plasma levels of the hormones cortisol and prolactin at those times. These hormones are good indicators of serotonergic functioning in the central nervous system.
Read more
We expect that patients with lower levels of serotonergic functioning will have more severe behavioural disturbances and be less responsive to treatment with citalopram. Following their first test day, we will provide patients with a 6-week supply of citalopram, and assess them for any changes in behaviour at the end of this treatment.
This study aims to obtain a better understanding of how changes in the serotonin system relate to behavioural symptoms in FTLD patients. Using the information from this pilot study, we can plan a larger study to determine whether certain behaviours will respond to treatment with citalopram, and if so, determine whether it is possible to predict which patients, based on individual characteristics, are most likely to respond to this treatment. This methodology will therefore not only provide a scientific rationale for treatment of FTLD, but also provide guidance for ongoing, individualized therapy.
Read the detailed description
Objectives: A hallmark of frontotemporal lobar degeneration(FTLD) is its associated behavioural disturbances (BPSD), which include disinhibition, aggression, apathy, agitation, depression, and inappropriate affect. Current evidence suggests that secondary changes in the serotonergic system may be key to many of the symptoms of FTLD. Our primary objective is to evaluate the ability of serotonergic dysfunction, as measured through oral citalopram challenge, to predict subsequent behavioural response to pharmacotherapy with citalopram. As a secondary objective, we will explore the relationship between specific BPSDs and the level of serotonergic dysfunction.
Hypotheses: We predict that patients with FTLD who respond to citalopram pharmacotherapy will show greater dysfunction in the serotonergic system, as measured by citalopram challenge, than patients who do not respond. This hypothesis will be evaluated in vivo using peak change in plasma concentrations of cortisol and prolactin as indicators of serotonergic dysfunction following oral citalopram challenge.
Research Plan: A consecutive sample of patients attending FTLD clinics who exhibit significant BPSD will be recruited into this study.Because serotonin promotes cortisol and prolactin secretion via the hypothalamic-pituitary-adrenal (HPA) axis, these hormones have been shown to be a reliable marker of serotonergic functioning. Their levels will therefore be measured from blood samples taken at baseline and 2 and 3 hours after the administration of 20 mg citalopram. Changes in cortisol levels after citalopram administration will be used as the primary measure of serotonergic functioning. We expect to find an inverse correlation between the cortisol response to citalopram challenge and the severity of BPSD according to the total Neuropsychiatric Inventory (NPI) score. Subsequent to the citalopram challenge, participants will be treated for their BPSD with open-label citalopram (20-40 mg) for 6 weeks. At the end of this period, patients will be re-assessed with the NPI. The magnitude of response, based on changes in NPI scores, will be correlated with the citalopram challenge test results. It is expected that patients who show more severe serotonergic dysfunction will have a better response to daily citalopram treatment.
Relevance: The results of this study will further the scientific understanding of the neurochemical basis underlying BPSD in FTLD. To date, the treatment of FTLD patients has relied largely on the understanding of treatments for other dementias, due to the lack of research in the area of FTLD. Therefore, our work may aid in the development of targeted therapies specific to FTLD.
- Conditions
- Frontotemporal Dementia
- Being tested
- Citalopram
- Keywords
- frontotemporal lobar degeneration, frontotemporal dementia, serotonin, dementia, behavioural disturbances
- Medical subject headings
- Frontotemporal Dementia, Frontotemporal Lobar Degeneration, Dementia, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CitalopramDrug
Titrates from 10mg/day to 40mg/day, increases 10mg per week.
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuropsychiatric Inventory (NPI)
Measured: Screening, Baseline, 4 weeks and 6 weeks
Secondary outcomes (5)
Frontal Behavioural Inventory (FBI)
Measured: Baseline, 4 weeks, 6 weeks
Clinical Global Impression (CGI)
Measured: Screening, 4 week, 6 week
Cornell Scale for Depression in Dementia
Measured: Baseline, 4 weeks and 6 weeks
Disability Assessment for Dementia Scale (DAD)
Measured: Baseline, 4 weeks and 6 weeks
Functional Assessment Staging (FAST)
Measured: Baseline, 4 weeks and 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2006 (estimated)
- Study startSep 2006
- Primary completionJul 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Frontotemporal DementiaStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Alzheimer Society of Canada
- Investigators
- Krista Lanctot, PhD, Principal investigator, Sunnybrook Health Sciences CentreNathan Herrmann, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00376051
- Sponsor's protocol ID
- 218-2006
- Other IDs
- 07-48
- Status last verified
- Nov 2009
- First submitted
- 13 Sep 2006
- Last updated
- 5 May 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Herrmann N, Black SE, Chow T, Cappell J, Tang-Wai DF, Lanctot KL. Serotonergic function and treatment of behavioral and psychological symptoms of frontotemporal dementia. Am J Geriatr Psychiatry. 2012 Sep;20(9):789-97. doi: 10.1097/JGP.0b013e31823033f3.
PubMed 21878805
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia
- ClinicalTrials.gov ID
- NCT00376051
- Acronym / sponsor ID
- 218-2006
- Conditions
- Frontotemporal Dementia
- Keywords
- frontotemporal lobar degeneration, frontotemporal dementia, serotonin, dementia, behavioural disturbances
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- Alzheimer Society of Canada
- Study start
- Sep 2006
- Primary completion
- Jul 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 14 Sep 2006 (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.
Frontotemporal lobar degeneration(FTLD) is a common cause of early-onset dementia. FTLD is characterized multiple behavioral symptoms including mental rigidity, irritability, emotional blunting, disinhibition, apathy, and aggression. These behavioural disturbances are particularly important because they increase caregiver burden and may lead to earlier institutionalization. While the causes of FTLD are largely unknown, there is a great deal of evidence suggesting that a brain chemical called serotonin regulates many of the behaviours that are disturbed in FTLD. Our objective is therefore to determine whether dysfunction in the brain's serotonin system is responsible for behavioural problems among FTLD patients. We hope to take the first steps towards a scientific understanding of the behavioural symptoms of FTD, and use our findings to support a larger study optimizing the treatment of targeted behavioural disturbances in FTLD using the antidepressant citalopram.
Citalopram increases transmission by serotonin; we plan to use this medication to determine whether there are any differences in how the serotonin system functions in FTLD patients who display different levels of behavioural disturbances. Patients will be given citalopram and will have their blood drawn after 2 and 3 hours to determine plasma levels of the hormones cortisol and prolactin at those times. These hormones are good indicators of serotonergic functioning in the central nervous system.
We expect that patients with lower levels of serotonergic functioning will have more severe behavioural disturbances and be less responsive to treatment with citalopram. Following their first test day, we will provide patients with a 6-week supply of citalopram, and assess them for any changes in behaviour at the end of this treatment.
This study aims to obtain a better understanding of how changes in the serotonin system relate to behavioural symptoms in FTLD patients. Using the information from this pilot study, we can plan a larger study to determine whether certain behaviours will respond to treatment with citalopram, and if so, determine whether it is possible to predict which patients, based on individual characteristics, are most likely to respond to this treatment. This methodology will therefore not only provide a scientific rationale for treatment of FTLD, but also provide guidance for ongoing, individualized therapy.
Detailed description
Objectives: A hallmark of frontotemporal lobar degeneration(FTLD) is its associated behavioural disturbances (BPSD), which include disinhibition, aggression, apathy, agitation, depression, and inappropriate affect. Current evidence suggests that secondary changes in the serotonergic system may be key to many of the symptoms of FTLD. Our primary objective is to evaluate the ability of serotonergic dysfunction, as measured through oral citalopram challenge, to predict subsequent behavioural response to pharmacotherapy with citalopram. As a secondary objective, we will explore the relationship between specific BPSDs and the level of serotonergic dysfunction.
Hypotheses: We predict that patients with FTLD who respond to citalopram pharmacotherapy will show greater dysfunction in the serotonergic system, as measured by citalopram challenge, than patients who do not respond. This hypothesis will be evaluated in vivo using peak change in plasma concentrations of cortisol and prolactin as indicators of serotonergic dysfunction following oral citalopram challenge.
Research Plan: A consecutive sample of patients attending FTLD clinics who exhibit significant BPSD will be recruited into this study.Because serotonin promotes cortisol and prolactin secretion via the hypothalamic-pituitary-adrenal (HPA) axis, these hormones have been shown to be a reliable marker of serotonergic functioning. Their levels will therefore be measured from blood samples taken at baseline and 2 and 3 hours after the administration of 20 mg citalopram. Changes in cortisol levels after citalopram administration will be used as the primary measure of serotonergic functioning. We expect to find an inverse correlation between the cortisol response to citalopram challenge and the severity of BPSD according to the total Neuropsychiatric Inventory (NPI) score. Subsequent to the citalopram challenge, participants will be treated for their BPSD with open-label citalopram (20-40 mg) for 6 weeks. At the end of this period, patients will be re-assessed with the NPI. The magnitude of response, based on changes in NPI scores, will be correlated with the citalopram challenge test results. It is expected that patients who show more severe serotonergic dysfunction will have a better response to daily citalopram treatment.
Relevance: The results of this study will further the scientific understanding of the neurochemical basis underlying BPSD in FTLD. To date, the treatment of FTLD patients has relied largely on the understanding of treatments for other dementias, due to the lack of research in the area of FTLD. Therefore, our work may aid in the development of targeted therapies specific to FTLD.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Meet the DSM-IV criteria for primary degenerative dementia
- Meet standard clinical criteria for frontotemporal dementia (ie., frontotemporal degeneration including both the frontal/behavioural variant and primary progressive aphasia)
- Have significant behavioural problems as demonstrated by a score of at least eight on the Neuropsychiatric Inventory (NPI) an
- An independent clinical decision to receive psychotropic medication for behavioural disorders
Key exclusion criteria (9 listed)
- An abnormal biochemical screening (blood cell count, vitamin B12 or thyroid function tests)
- Significant medical illness or other medical/neurological conditions which diminish cognitive function (including: drug overdose, severely disturbed liver, kidney, lung or heart function, anemia, hypothyroidism, vitamin B12 or folic acid deficiency, syphilis, uncontrolled diabetes, Parkinson's disease, Huntington's chorea, progressive supranuclear paralysis, brain tumour, subdural hematoma, multiple sclerosis, or brain trauma);
- An Hachinski ischemic score ≥444;
- Electrocardiographic, laboratory or physical evidence of significant cardiovascular disease;
- Hypertension >160 mmHg systolic or >100 mmHg diastolic;
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 |
|---|---|---|
| CitalopramTitrates from 10mg/day to 40mg/day, increases 10mg per week. | Drug | – |
Primary outcome
Neuropsychiatric Inventory (NPI)
Time frame: Screening, Baseline, 4 weeks and 6 weeks
5 secondary outcomes
Frontal Behavioural Inventory (FBI)
Time frame: Baseline, 4 weeks, 6 weeks
Clinical Global Impression (CGI)
Time frame: Screening, 4 week, 6 week
Cornell Scale for Depression in Dementia
Time frame: Baseline, 4 weeks and 6 weeks
Disability Assessment for Dementia Scale (DAD)
Time frame: Baseline, 4 weeks and 6 weeks
Functional Assessment Staging (FAST)
Time frame: Baseline, 4 weeks and 6 weeks
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 May 2017.
- Results publication: PubMed 21878805Herrmann N, Black SE, Chow T, Cappell J, Tang-Wai DF, Lanctot KL. Serotonergic function and treatment of behavioral and psychological symptoms of frontotemporal dementia. Am J Geriatr Psychiatry. 2012 Sep;20(9):789-97. doi: 10.1097/JGP.0b013e31823033f3.
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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.
Krista Lanctot, PhD principal investigator
Sunnybrook Health Sciences Centre
Nathan Herrmann, MD principal investigator
Sunnybrook Health Sciences Centre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Citalopram in people with Frontotemporal Dementia, run by Sunnybrook Health Sciences Centre at 2 sites in Canada.
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 4 inclusion and 9 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 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
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?
Neuropsychiatric Inventory (NPI) (time frame: Screening, Baseline, 4 weeks and 6 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 NCT00376051, which also lists 1 linked publication.
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 May 2017.