A Genetic and Perfusion Study of Response to Cognitive Enhancers in Lewy Body Disease

NCT01944436 | Completed

• 1 other identifier: LBD-312-2006
• Study Type: observational
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

Lewy body spectrum disorders are a common group of neurodegenerative diseases that cause memory loss, behavioural and motor disabilities that impair quality of life. Cognitive enhancers help people afflicted with these conditions. However, some people do not benefit from this treatment, while others experience serious side effects. Side effects and poor response lead to hospitalization and early institutionalization. Pharmacogenomics, the study of how DNA variation can influence drug effects, will be combined with functional changes in brain imaging in response to cognitive enhancers in patients with Lewy body disease. The goal is to develop a predictive test that can be administered in the clinic to aid physicians' choice of initial medication. This can reduce health care costs and improve treatment to Canadians suffering from these devastating disorders.

Conditions

Lewy Body Disease

Keywords

Pharmacogenomics; Dementia with Lewy bodies; Adverse events; Polymorphisms; Acetylcholinesterase; Parkinson's Disease Dementia; Cognitive enhancers; Clinical efficacy; Cytochrome P450; Butyrylcholinesterase

Outcome Measures

Primary Outcomes (2)

• Change from baseline in perfusion brain SPECT at 6 months

  0 and 6 months

• Change from baseline in neuropsychological assessment scores at 6 months

  0 and 6 months

Secondary Outcomes (1)

• Volumetric Brain MRI

  Baseline

Study Arms (2)

Parkinson's Disease Dementia

Participants in the Parkinson's Disease Dementia group: * Must be taking a stable parkinsonian medication * Must have a diagnosis of clinically definite Parkinson's disease \>1 year prior to cognitive deficit with at least two of the following symptoms: asymmetric resting tremor, rigidity or bradykinesia, and definite motor response to dopaminergic agents. * Response to cholinesterase inhibitor over a period of six months will be monitored.

Drug: Cholinesterase Inhibitors (Rivastigmine, Aricept, Galantamine)

Dementia with Lewy Bodies

Participants in the Dementia with Lewy Bodies group: * Diagnosis of clinically probable or possible Dementia with Lewy bodies with at least 1 of the following: Marked fluctuations in cognition, visual hallucinations or spontaneous parkinsonism. * Response to cholinesterase inhibitor over a period of six months will be monitored.

Drug: Cholinesterase Inhibitors (Rivastigmine, Aricept, Galantamine)

Interventions

Cholinesterase Inhibitors (Rivastigmine, Aricept, Galantamine) DRUG

Dementia with Lewy Bodies; Parkinson's Disease Dementia

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Ontario, Canada.

You may not qualify if:

• age \< 50; Severe dementia (MMSE \< 9); contact \< 4 days a week with a responsible caregiver; Hoehn \& Yahr stage \> 4.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

Biospecimen

Retention: SAMPLES WITH DNA

Functional and tag SNPs in the following genes will be assessed: acetylcholinesterase (ACHE); butyrylcholinesterase (BCHE); M1 muscarinic receptor (CHRM1); alpha7-nicotinic receptor (CHRNA7); Apolipoprotein E (ApoE); Cytochrome P450 2D6 (protein: CYP2D6 /gene: CYP2D6); CYP3A4; all genes related to blood pressure disregulation, white matter changes found on neuroimaging, and genes related to Lewy Body Spectrum disorders in general.

MeSH Terms

Conditions

Lewy Body Disease; Pain; Butyrylcholinesterase deficiency

Interventions

Cholinesterase Inhibitors; Rivastigmine; Donepezil; Galantamine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Phenylcarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Amaryllidaceae Alkaloids; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician-Scientist

Study Record Dates

• First Submitted: September 10, 2013
• First Posted: September 17, 2013
• Study Start: September 1, 2006
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: April 13, 2016

Record last verified: 2016-04

Locations

CA (1)