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Sponsors and Collaborators: |
Sunnybrook Health Sciences Centre Alzheimer Society of Canada |
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Information provided by: | Sunnybrook Health Sciences Centre |
ClinicalTrials.gov Identifier: | NCT00376051 |
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.
Condition | Intervention | Phase |
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Frontotemporal Dementia |
Drug: Citalopram |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study |
Official Title: | Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia |
Estimated Enrollment: | 22 |
Study Start Date: | September 2006 |
Estimated Study Completion Date: | November 2008 |
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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Krista Lanctot | 416-480-6100 ext 2241 | krista.lanctot@sunnbrook.ca |
Contact: Ryan Rajaram | 416-480-6100 ext 3185 | ryan.rajaram@sri.utoronto.ca |
Canada, Ontario | |
Sunnybrook Health Sciences Centre | Recruiting |
Toronto, Ontario, Canada, M4N 3M5 | |
Contact: Ryan Rajaram, MSc 416-480-6100 ext 3185 ryan.rajaram@sri.utoronto.ca | |
Contact: Lana Rothenburg, Hon. B.Sc 416-480-6100 ext 3185 lana.rothenburg@sunnybrook.ca | |
The Baycrest Centre for Geriatric Care | Recruiting |
Toronto, Ontario, Canada, M6A 2E1 | |
Contact: Tiffany Chow, MD 416-785-2500 ext 3459 tchow@rotman-baycrest.on.ca |
Principal Investigator: | Krista Lanctot, PhD | Sunnybrook Health Sciences Centre |
Principal Investigator: | Nathan Herrmann, MD | Sunnybrook Health Sciences Centre |
Study ID Numbers: | 218-2006, 07-48 |
Study First Received: | September 13, 2006 |
Last Updated: | May 21, 2008 |
ClinicalTrials.gov Identifier: | NCT00376051 |
Health Authority: | Canada: Health Canada |
frontotemporal lobar degeneration frontotemporal dementia serotonin dementia behavioural disturbances |
Pick Disease of the Brain Speech Disorders Frontotemporal dementia Aphasia Central Nervous System Diseases Language Disorders Brain Diseases Citalopram Aphasia, Primary Progressive Serotonin Cognition Disorders Signs and Symptoms |
Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders Neurologic Manifestations Lobar atrophy of brain Primary progressive aphasia Dexetimide Dementia Neurobehavioral Manifestations Pick disease of the brain Communication Disorders Delirium |
Neurotransmitter Uptake Inhibitors Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Nervous System Diseases Physiological Effects of Drugs Psychotropic Drugs Serotonin Uptake Inhibitors |
Pharmacologic Actions Serotonin Agents Therapeutic Uses Antidepressive Agents, Second-Generation Central Nervous System Agents Antidepressive Agents |