Citalopram as a Posterior Cortical Protective Therapy in Parkinson Disease

Phase 2

Active, not recruiting

• Conditions: Parkinson Disease
• Interventions: Drug: Citalopram 20mg; Drug: Placebo

• Registration Number: NCT04497168
• Lead Sponsor: University of Michigan

Brief Summary

This Parkinson disease (PD) trial will test whether 26 months of citalopram, compared to placebo, can alter the build-up of toxic amyloid-beta plaques in the visuospatial cortex of the brain linked to visuospatial cognitive impairment in PD.

Detailed Description

This study is a proof-of-concept Parkinson disease trial aimed at delaying visuospatial cognitive decline, an important component of Parkinson dementia. In Parkinson disease, low-range cortical Abeta plaque levels associate with serotonin terminal losses. Multicenter Parkinson disease observational findings show that selective serotonin reuptake inhibitors (SSRIs) associate with lower dementia conversion risk and different cerebrospinal fluid Abeta-42 levels. This study aims to test the hypothesis that citalopram use in Parkinson disease will reduce visuospatial cortex Abeta plaque accrual, leading to an amelioration of longitudinal visuospatial cognitive decline linked to Parkinsonian dementia. The study will test this hypothesis in a randomized placebo-controlled trial of citalopram 20mg daily over 26 months in Parkinson disease subjects (age ≥65) without depression (n=58).

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-07-29
• Study First Submitted QC: 2020-07-29
• Study First Posted: 2020-08-04
• Study Start: 2021-04-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-08
• Last Update Posted: 2024-03-12
• Primary Completion: 2026-03-01
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

• Subjects with a Parkinson Disease (PD) diagnosis based on the United Kingdom Parkinson's Disease Society Brain Bank Research Center clinical diagnostic criteria
• Modified Hoehn and Yahr (HY) scores spanning 2.0 to 3.0
• Age 65 years or greater

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Exclusion Criteria

• Diagnosis of an atypical parkinsonian condition
• Participants on neuroleptics and participants with a history of use of anti-depressants (including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), bupropion, St. John's Wort or other serotoninergic agents in the year preceding study enrollment
• Evidence of a large artery stroke or mass lesion on brain imaging
• Participants with a life threatening comorbid illness
• Severe claustrophobia precluding PET imaging
• Inability to participate in research procedures involving ionizing radiation
• Pregnancy or breastfeeding
• Participants with active depression as defined by a Geriatric Depression Scale score of >10 or on the basis of clinical diagnosis by the PI
• Participants who report active suicidal ideation as defined by an affirmative answer to questions 1 and 2 on the C-SSRS
• Participants with baseline HY scores <2.0 or ≥3.0
• Participants with a QTc interval on baseline EKG >0.45 for men or >0.47 for women
• Subjects taking certain contraindicated medications at baseline
• Subjects unable to swallow pills
• Subjects with a previous history of mania, ongoing hepatic impairment or epilepsy
• Subjects with a known allergy to citalopram or escitalopram
• Subjects with substantial cognitive impairment or dementia that would prevent them from providing informed consent
• Subjects in another ongoing clinical trial
• Subjects with treatment-naieve Parkinson disease

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Citalopram	Citalopram 20mg	20mg daily
Placebo	Placebo	matching placebo pills

Primary Outcome Measures

Name	Time	Method
Change in visuospatial cortex PiB distribution volume ratio (DVR)	Baseline to month 26	PiB PET can assess the density of amyloid-beta plaques in the brain. This imaging method will be used to quantify the amount of change in amyloid-beta plaques levels--measured specifically within the visuospatial cortex--between month 0 and month 26.

Secondary Outcome Measures

Name	Time	Method
Change in Benton Judgement of Line Orientation (JOLO) test score	Baseline to month 26	This is a standardized test with 30 items that is specific for visual spatial cognition. The minimum score is 0, indicating low visual spatial cognition. The maximum score is 30, indicating high visual spatial cognition.
Change in Montreal Cognitive Assessment (MoCA) score	Baseline to month 26	This scale evaluates different domains of cognition like attention, orientation, memory, language, visuoconstructional capacities, and lastly, executive functions. MoCA is a 30 point test with lower scores indicating impaired cognition. The maximum score is 30.

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States