Citalopram as a Posterior Cortical Protective Therapy in Parkinson Disease

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Citalopram 20mg; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Citalopram; 20mg daily	Drug: Citalopram 20mg; 20mg daily
Placebo Comparator: Placebo; matching placebo pills	Drug: Placebo; matching placebo pills

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in visuospatial cortex PiB distribution volume ratio (DVR)	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.	Baseline to month 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Benton Judgement of Line Orientation (JOLO) test score	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.	Baseline to month 26
Change in Montreal Cognitive Assessment (MoCA) score	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.	Baseline to month 26

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Vikas Kotagal, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: July 29, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Serotonin; Selective Serotonin Reuptake Inhibitor; Amyloid-beta
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Selective Serotonin Reuptake Inhibitors; Citalopram
• Other Study ID Numbers: HUM00146905; 1R01AG065246 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Participant data will be uploaded in a timely manner in the "openICPSR" Data Management Resource (DMR) of ICPSR (Inter-University Consortium for Political and Social Research). Biospecimens (DNA) will be banked in the NIA NCRAD biorepository. Uploaded datasets will be stripped of identifiers in order to prevent the possibility of identifying human subjects participants in this study from the publically available dataset.
• IPD Sharing Time Frame: Consistent with NIA policies, the study team will ensure the dataset is shared by the occurrence of the earlier of the following two milestones: either the date of primary publication or within 9 months of lifting of the data lock.
• IPD Sharing Access Criteria: Access to the coded dataset that is uploaded to openICPSR is available to any individual who applies to the openICPSR for data access. This process involves providing a brief description of the intended use of the data to be downloaded, a data use agreement and data security plan, and documentation of IRB approval or exemption.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No