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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Sunnybrook Health Sciences Centre
Sponsor:
Information provided by (Responsible Party):
Dr. Mario Masellis, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:
NCT01944436
First received: September 10, 2013
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention
Lewy Body Disease
Drug: Cholinesterase Inhibitors (Rivastigmine, Aricept, Galantamine)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Lewy Body Spectrum Disorders: Investigating Neuropsychiatric Benefit and Adverse Effects in Response to Cholinesterase Inhibitors Using Genetics and Brain SPECT

Resource links provided by NLM:


Further study details as provided by Sunnybrook Health Sciences Centre:

Primary Outcome Measures:
  • Change from baseline in perfusion brain SPECT at 6 months [ Time Frame: 0 and 6 months ] [ Designated as safety issue: No ]
  • Change from baseline in neuropsychological assessment scores at 6 months [ Time Frame: 0 and 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Volumetric Brain MRI [ Time Frame: Baseline ] [ Designated as safety issue: No ]

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.


Estimated Enrollment: 180
Study Start Date: September 2006
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Ontario, Canada.

Criteria

Inclusion Criteria:

  • Inclusion criteria for patients with a Lewy body spectrum disorder includes: age > 50 years; and mild-moderate dementia (Mini-Mental State Exam [MMSE] > 9); contact on at least four of seven days/week with a responsible caregiver; Hoehn & Yahr stage ≤ 4.

Exclusion Criteria:

  • age < 50; Severe dementia (MMSE < 9); contact < 4 days a week with a responsible caregiver; Hoehn & Yahr stage > 4.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01944436

Contacts
Contact: Michelle A Messner, B.A. 416-480-6100 ext 1620 michelle.messner@sunnybrook.ca
Contact: Kayla Sherborn, B.A. 416-480-6100 ext 1620 kayla.sherborn@sunnybrook.ca

Locations
Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N3M5
Contact: Michelle Messner    416-480-6100 ext 1620    michelle.messner@sunnybrook.ca   
Contact: Kayla Sherborn    416-480-6100 ext 1620    kayla.sherborn@sunnybrook.ca   
Principal Investigator: Mario Masellis, MSc, MD, PhD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
  More Information

No publications provided

Responsible Party: Dr. Mario Masellis, Clinician-Scientist, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT01944436     History of Changes
Other Study ID Numbers: LBD-312-2006
Study First Received: September 10, 2013
Last Updated: September 12, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Sunnybrook Health Sciences Centre:
Pharmacogenomics
Dementia with Lewy bodies
Adverse events
Polymorphisms
Acetylcholinesterase
Parkinson's Disease Dementia
Cognitive enhancers
Clinical efficacy
Cytochrome P450
Butyrylcholinesterase

Additional relevant MeSH terms:
Lewy Body Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Movement Disorders
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Rivastigmine
Cholinesterase Inhibitors
Nootropic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 01, 2014