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Escitalopram Effects on CSF Amyloid Beta

Primary Purpose

Amyloid Beta Protein

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Escitalopram 20mg for 2 weeks
Escitalopram 20mg for 8 weeks
Escitalopram 30mg for 8 weeks
Placebo
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Amyloid Beta Protein focused on measuring Escitalopram, Amyloid Beta, Cerebrospinal Fluid

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

  • 1) Known history of relevant severe drug allergy or hypersensitivity (e.g. to Citalopram or Escitalopram)
  • 2) Does not speak English
  • 3) Cannot give informed consent
  • 4) Diagnosis of Major Depression
  • 5) Previous history of neurological disorders, such as Parkinson's disease, Alzheimer's disease or traumatic brain injury, cognitive impairment or dementia.
  • 6) Diagnosis of a chronic psychiatric illness
  • 7) Significant hearing or visual impairment
  • 8) Bleeding diathesis
  • 9) 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.
  • 10) 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.
  • 11) Clinically significant abnormalities on EKG. Primary AV block or Right bundle branch block are not necessarily exclusionary.
  • 12) History of drug or alcohol abuse within the last year or prior prolonged history of abuse
  • 13) Use of an Investigational medicine within the past 30 days 14) Use of Coumadin, Warfarin or other blood thinners within the past 6 months
  • 15) Use of antipsychotic medication or antidepressant medication (e.g. MAOIs, SSRIs, SNRIs).
  • 16) Use of the following drug/drug classes: Pimozide, Triptans, Tricyclics, Lithium, Tramadol
  • 17) 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)

Sites / Locations

  • Washington University
  • University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

Escitalopram 20mg for 2 weeks

Placebo (sugar pill)

Escitalopram 30mg for 8 weeks

Escitalopram 20mg for 8 weeks

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
June 5, 2014
Last Updated
April 6, 2020
Sponsor
University of Pennsylvania
Collaborators
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT02161458
Brief Title
Escitalopram Effects on CSF Amyloid Beta
Official Title
Escitalopram Effects on CSF Amyloid Beta Total Concentrations
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
January 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
Washington University School of Medicine

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
The investigators will measure CSF Amyloid Beta levels before and after two weeks or eight weeks of treatment with escitalopram using a double blind placebo-controlled study design with approximately 30 cognitively normal participants, age 60-85, with a MOCA of 23 or higher. They will be recruited from the community. Participants will be randomized (approximately 30 per group). Participants in the 2 week arm will have 3 study visits: Screening Visit: Consent and screening procedures will be complete. Participants will be randomized 1:1 to receive escitalopram or placebo. Study Visit 1: This visit will take approximately 45 minutes - 1 hour; participants will have a lumbar puncture (LP) in order to obtain cerebrospinal fluid (CSF), a blood draw, and will receive study medication. Study Visit 2: This visit will take approximately 45 minutes - 1 hour; participants will have a lumbar puncture (LP) in order to obtain cerebrospinal fluid (CSF), a blood draw, will receive taper-down study medication, and will complete an end-of-study questionnaire. Participants in the 8-week arm(s) will have 4 study visits: Screening Visit: Consent and screening procedures will be complete. Participants will be randomized 1:1 to receive escitalopram or placebo. Study Visit 1: This visit will take approximately 45 minutes - 1 hour; participants will have a lumbar puncture (LP) in order to obtain cerebrospinal fluid (CSF), a blood draw, and will receive 4 weeks of study medication. Study Visit 2: Researchers will check in with participants and participants will receive another 4 weeks of study medication. Study Visit 3:This visit will take approximately 45 minutes - 1 hour; participants will have a lumbar puncture (LP) in order to obtain cerebrospinal fluid (CSF), a blood draw, will receive taper-down study medication, and will complete an end-of-study questionnaire. The current proposal will test whether clinically relevant doses of an SSRI reduce CSF levels of Amyloid Beta in healthy older human participants. The investigators hypothesize that compared to placebo, participants receiving escitalopram will show significantly lower Amyloid Beta levels in the second CSF sample.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloid Beta Protein
Keywords
Escitalopram, Amyloid Beta, Cerebrospinal Fluid

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
98 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Escitalopram 20mg for 2 weeks
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo (sugar pill)
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Escitalopram 30mg for 8 weeks
Arm Type
Experimental
Arm Description
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.
Arm Title
Escitalopram 20mg for 8 weeks
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Escitalopram 20mg for 2 weeks
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Escitalopram 20mg for 8 weeks
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Escitalopram 30mg for 8 weeks
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Amyloid Beta Levels in CSF
Description
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.
Time Frame
2 - 8 Weeks (we used week 8 minus baseline and week 2 minus baseline)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 1) Age 60-85 (inclusive), male and female, any race. 2) Capacity to give informed consent and follow study procedures. 3) English speaking. 4) MOCA = 23 or greater Exclusion Criteria: 1) Known history of relevant severe drug allergy or hypersensitivity (e.g. to Citalopram or Escitalopram) 2) Does not speak English 3) Cannot give informed consent 4) Diagnosis of Major Depression 5) Previous history of neurological disorders, such as Parkinson's disease, Alzheimer's disease or traumatic brain injury, cognitive impairment or dementia. 6) Diagnosis of a chronic psychiatric illness 7) Significant hearing or visual impairment 8) Bleeding diathesis 9) 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. 10) 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. 11) Clinically significant abnormalities on EKG. Primary AV block or Right bundle branch block are not necessarily exclusionary. 12) History of drug or alcohol abuse within the last year or prior prolonged history of abuse 13) Use of an Investigational medicine within the past 30 days 14) Use of Coumadin, Warfarin or other blood thinners within the past 6 months 15) Use of antipsychotic medication or antidepressant medication (e.g. MAOIs, SSRIs, SNRIs). 16) Use of the following drug/drug classes: Pimozide, Triptans, Tricyclics, Lithium, Tramadol 17) 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yvette Sheline, M.D.
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32913021
Citation
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.
Results Reference
derived

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Escitalopram Effects on CSF Amyloid Beta

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