Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia

NCT00376051 | Completed Phase 4

• 2 other identifiers: 218-200607-48
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

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. 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.

Conditions

Frontotemporal Dementia

Keywords

frontotemporal lobar degeneration; frontotemporal dementia; serotonin; dementia; behavioural disturbances

Outcome Measures

Primary Outcomes (1)

• Neuropsychiatric Inventory (NPI)

  Screening, Baseline, 4 weeks and 6 weeks

Secondary Outcomes (5)

• Frontal Behavioural Inventory (FBI)

  Baseline, 4 weeks, 6 weeks

• Clinical Global Impression (CGI)

  Screening, 4 week, 6 week

• Cornell Scale for Depression in Dementia

  Baseline, 4 weeks and 6 weeks

• Disability Assessment for Dementia Scale (DAD)

  Baseline, 4 weeks and 6 weeks

• Functional Assessment Staging (FAST)

  Baseline, 4 weeks and 6 weeks

Interventions

Citalopram DRUG

Titrates from 10mg/day to 40mg/day, increases 10mg per week.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Alzheimer Society of Canada: collaborator

Study Sites (2)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

The Baycrest Centre for Geriatric Care

Toronto, Ontario, M6A 2E1, Canada

Location

Related Publications (1)

• 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.

  PMID: 21878805 RESULT

MeSH Terms

Conditions

Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Dementia; Mental Disorders

Interventions

Citalopram

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Krista Lanctot, PhD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• Nathan Herrmann, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 13, 2006
• First Posted: September 14, 2006
• Study Start: September 1, 2006
• Primary Completion: July 1, 2009
• Study Completion: September 1, 2009
• Last Updated: May 5, 2017

Record last verified: 2009-11

Locations

CA (2)