Escitalopram Effects on CSF Amyloid Beta

NCT02161458 | Completed Phase 4 Results

• 1 other identifier: R01AG041502
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 2

Brief Summary

Alzheimers disease (AD) is a devastating illness, estimated to affect 5 million patients in the United States alone and projected to increase dramatically over the next decades as the population ages unless preventive measures can be developed. The investigators have preliminary evidence that selective serotonin reuptake inhibitor (SSRI) antidepressants lower the amount of amyloid plaques in the human brain. The interventions now propose to study the effects of an SSRI (escitalopram) on levels of amyloid beta peptide (the major constituent of the plaques) in the cerebrospinal fluid (CSF) of cognitively normal older adults.

Conditions

Amyloid Beta Protein

Keywords

Escitalopram; Amyloid Beta; Cerebrospinal Fluid

Outcome Measures

Primary Outcomes (1)

• Amyloid Beta Levels in CSF

  Change in the level of Amyloid Beta peptides (Amyloid Beta 42 and Amyloid Beta 40) in the CSF between the measurement at baseline and the measurement after exposure with escitalopram.

  2 - 8 Weeks (we used week 8 minus baseline and week 2 minus baseline)

Study Arms (4)

Escitalopram 20mg for 2 weeks

EXPERIMENTAL

30 cognitively normal adults aged 60-85 will receive escitalopram 20mg for 2 weeks (upward titration as: 10mg for 5 days, then 20mg for 9 days); and amyloid beta levels in the CSF will be measured at baseline (before drug administration) and after 2 weeks of study drug (active or placebo). Participants will taper off medication following the 2nd CSF measurement.

Drug: Escitalopram 20mg for 2 weeks

Placebo (sugar pill)

PLACEBO COMPARATOR

30 cognitively normal adults aged 60-85 will receive placebo for 2 weeks (upward titration as: 10mg for 5 days, then 20mg for 9 days) or 8 weeks (upward titration as: 10mg for 5 days, then 20mg for 51 days); and amyloid beta levels in the CSF will be measured at baseline (before drug administration) and after 2 or 8 weeks of study drug (active or placebo). Participants will taper off medication following the 2nd CSF measurement.

Drug: Placebo

Escitalopram 30mg for 8 weeks

EXPERIMENTAL

30 cognitively normal adults aged 60-85 will receive escitalopram 30 mg for 8 weeks (upward titration as: 10mg for 5 days, then 20mg for 5 days; then 30 mg for 46 days); and amyloid beta levels in the CSF will be measured at baseline (before drug administration) and after 8 weeks of study drug (active or placebo). Participants will taper off medication following the 2nd CSF measurement.

Drug: Escitalopram 30mg for 8 weeks

Escitalopram 20mg for 8 weeks

EXPERIMENTAL

30 cognitively normal adults aged 60-85 will receive escitalopram 20mg for 8 weeks (upward titration as: 10mg for 5 days, then 20mg for 51 days); and amyloid beta levels in the CSF will be measured at baseline (before drug administration) and after 8 weeks of study drug (active or placebo). Participants will taper off medication following the 2nd CSF measurement.

Drug: Escitalopram 20mg for 8 weeks

Interventions

Escitalopram 20mg for 2 weeks DRUG

30 cognitively normal adults aged 60-85 will receive escitalopram 20 mg for 2 weeks; amyloid beta levels in the CSF will be measured at baseline (before drug administration) and following the full study drug (i.e., active drug) administration.

Escitalopram 20mg for 2 weeks

Escitalopram 20mg for 8 weeks DRUG

30 cognitively normal adults aged 60-85 will receive escitalopram 20 mg for 8 weeks; amyloid beta levels in the CSF will be measured at baseline (before drug administration) and following the full study drug (i.e., active drug) administration.

Escitalopram 20mg for 8 weeks

Escitalopram 30mg for 8 weeks DRUG

30 cognitively normal adults aged 60-85 will receive escitalopram 30 mg for 8 weeks; amyloid beta levels in the CSF will be measured at baseline (before drug administration) and following the full study drug (i.e., active drug) administration.

Escitalopram 30mg for 8 weeks

Placebo DRUG

Additionally, 30 cognitively normal adults aged 60-85 will receive a placebo; amyloid beta levels in the CSF will be measured at baseline (before drug administration) and following the full study drug (i.e., placebo) administration.

Placebo (sugar pill)

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Age 60-85 (inclusive), male and female, any race.
• \) Capacity to give informed consent and follow study procedures.
• \) English speaking.
• \) MOCA = 23 or greater

You may not qualify if:

• \) Known history of relevant severe drug allergy or hypersensitivity (e.g. to Citalopram or Escitalopram)
• \) Does not speak English
• \) Cannot give informed consent
• \) Diagnosis of Major Depression
• \) Previous history of neurological disorders, such as Parkinson's disease, Alzheimer's disease or traumatic brain injury, cognitive impairment or dementia.
• \) Diagnosis of a chronic psychiatric illness
• \) Significant hearing or visual impairment
• \) Bleeding diathesis
• \) Clinically significant hepatic, renal, pulmonary, metabolic or endocrine disturbances as indicated by history, which in the opinion of the investigator might pose a potential safety risk to the subject.
• \) Current clinically significant cardiovascular disease. Clinically significant cardiovascular disease usually includes one or more of the following: cardiac surgery or myocardial infarction within the last 4 weeks; unstable angina; acute decompensated congestive heart failure or class IV heart failure; current significant cardiac arrhythmia or conduction disturbance, particularly those resulting in ventricular fibrillation, or causing syncope or near syncope; uncontrolled high blood pressure; QTc greater than 450msec (by history for subjects with cardiac disease); documented prior stroke.
• \) History of drug or alcohol abuse within the last year or prior prolonged history of abuse
• \) Use of an Investigational medicine within the past 30 days 14) Use of Coumadin, Warfarin or other blood thinners within the past 6 months
• \) Use of antipsychotic medication or antidepressant medication (e.g. MAOIs, SSRIs, SNRIs).
• \) Use of the following drug/drug classes: Pimozide, Triptans, Tricyclics, Lithium, Tramadol
• \) Use of over-the-counter supplements such as tryptophan or St. Johns Wort 18) Any other factor that in the investigator's judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from the research institution)

Sponsors & Collaborators

• University of Pennsylvania: lead
• Washington University School of Medicine: collaborator

Study Sites (2)

Washington University

St Louis, Missouri, 63110, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Sheline YI, Snider BJ, Beer JC, Seok D, Fagan AM, Suckow RF, Lee JM, Waligorska T, Korecka M, Aselcioglu I, Morris JC, Shaw LM, Cirrito JR. Effect of escitalopram dose and treatment duration on CSF Abeta levels in healthy older adults: A controlled clinical trial. Neurology. 2020 Nov 10;95(19):e2658-e2665. doi: 10.1212/WNL.0000000000010725. Epub 2020 Sep 10.

  PMID: 32913021 DERIVED

MeSH Terms

Conditions

Plaque, Amyloid

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Yvette Sheline, Principal Investigator
• Organization: University of Pennsylvania

cndslab@pennmedicine.upenn.edu

215-746-2637

Study Officials

• Yvette Sheline, M.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2014
• First Posted: June 11, 2014
• Study Start: June 1, 2014
• Primary Completion: August 1, 2017
• Study Completion: January 1, 2019
• Last Updated: April 9, 2020
• Results First Posted: March 12, 2019

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)