Clinical Trial: Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia

Brief 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. 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.

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. Subse
Sponsor: Sunnybrook Health Sciences Centre

Current Primary Outcome: Neuropsychiatric Inventory (NPI) [ Time Frame: Screening, Baseline, 4 weeks and 6 weeks ]

Original Primary Outcome: Neuropsychiatric Inventory (NPI)

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

  • Frontal Behavioural Inventory (FBI)
  • Clinical Global Impression (CGI)
  • Cornell Scale for Depression in Dementia
  • Disability Assessment for Dementia Scale (DAD)
  • Functional Assessment Staging (FAST)


Information By: Sunnybrook Health Sciences Centre

Dates:
Date Received: September 13, 2006
Date Started: September 2006
Date Completion:
Last Updated: May 2, 2017
Last Verified: November 2009