Citalopram as a Posterior Cortical Protective Therapy in Parkinson Disease

University of Michigan

Status and phase: Active, not recruiting; Phase 2

Conditions: Parkinson Disease

Treatments: Drug: Placebo; Drug: Citalopram 20mg

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04497168

1R01AG065246 (U.S. NIH Grant/Contract)

HUM00146905

Details and patient eligibility

About

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.

Full 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).

Enrollment: 58 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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58 participants in 2 patient groups, including a placebo group

Citalopram

Experimental group

Description:

20mg daily

Treatment:

Drug: Citalopram 20mg

Placebo

Placebo Comparator group

Description:

matching placebo pills

Treatment:

Drug: Placebo