CompletedNCT02161458Updated Apr 9, 2020Results posted

Escitalopram Effects on CSF Amyloid Beta

A Phase 4 interventional study of Escitalopram 20mg for 2 weeks and Escitalopram 20mg for 8 weeks in Amyloid Beta Protein, sponsored by University of Pennsylvania. Completed at 2 sites in United States. Open to participants aged 60 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-04-09.

Sponsored by University of Pennsylvania · Phase 4, Interventional, and Health services research

Phase: Phase 4
Study type: Interventional
Enrollment: 98
Allocation: Randomized
Ages: 60 Years to 85 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Amyloid Beta Protein

Browse trials for

Amyloidosis 491

Keywords

Escitalopram
Amyloid Beta
Cerebrospinal Fluid

In context

Amyloidosis

491 studies on the registry are indexed under Amyloidosis; 135 are open to participants now.

This study's enrollment of 98 is above the median of 40 across 304 interventional studies indexed under Amyloidosis.

Browse Amyloidosis studies →

Lead sponsor

University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 60 Years to 85 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

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

Study design

Phase: Phase 4
Primary purpose: Health services research
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 98 participants (actual)

Study arms

Experimental
Escitalopram 20mg for 2 weeks
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 comparator
Placebo (sugar pill)
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
Experimental
Escitalopram 30mg for 8 weeks
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
Experimental
Escitalopram 20mg for 8 weeks
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

DrugEscitalopram 20mg for 2 weeks
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.
DrugEscitalopram 20mg for 8 weeks
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.
DrugEscitalopram 30mg for 8 weeks
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.
DrugPlacebo
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.

What researchers measure

Primary outcomes

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.
Time frame: 2 - 8 Weeks (we used week 8 minus baseline and week 2 minus baseline)

Results

Posted Mar 12, 2019

Participant flow

Participant flow — Overall Study
Milestone	Escitalopram 20mg for 2 Weeks	Placebo (Sugar Pill)	Escitalopram 30mg for 8 Weeks	Escitalopram 20mg for 8 Weeks
Started	22	35	33	8
Completed	22	29	28	8
Not completed	0	6	5	0
Withdrew: Withdrawal by subject	0	4	4	0
Withdrew: Lost to follow-up	0	2	1	0

Outcome measures

PrimaryAmyloid 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.

Time frame:: 2 - 8 Weeks (we used week 8 minus baseline and week 2 minus baseline)
Reported as:: Mean · pg/mL

Amyloid Beta Levels in CSF
pg/mL	Escitalopram 20mg for 2 Weeks	Placebo (Sugar Pill)	Escitalopram 30mg for 8 Weeks	Escitalopram 20mg for 8 Weeks
Ab 42 in CSF	-12.7 ± 24.43	6.74 ± 45.16	-22.73 ± 43.80	-25.63 ± 23.29
Ab 40 in CSF	46.27 ± 539.29	197.36 ± 540.82	-152.64 ± 572.90	-41.82 ± 1039.83

Adverse events

Collected over Adverse Events were collected for up to 2 weeks after participants were active in the study, from the time of consent to the participant's last study visit.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Escitalopram 20mg for 2 Weeks	0/22 (0%)	0/22 (0%)	0/22 (0%)
Placebo (Sugar Pill)	0/29 (0%)	0/29 (0%)	0/29 (0%)
Escitalopram 30mg for 8 Weeks	0/28 (0%)	0/28 (0%)	0/28 (0%)
Escitalopram 20mg for 8 Weeks	0/8 (0%)	0/8 (0%)	0/8 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Escitalopram 20mg for 2 Weeks	Placebo (Sugar Pill)	Escitalopram 30mg for 8 Weeks	Escitalopram 20mg for 8 Weeks	Total
Mean	71 (60 to 79)	70 (59 to 83)	67 (60 to 78)	65 (60 to 70)	69 (59 to 83)

Sex: Female, Male
Sex: Female, Male(Participants)	Escitalopram 20mg for 2 Weeks	Placebo (Sugar Pill)	Escitalopram 30mg for 8 Weeks	Escitalopram 20mg for 8 Weeks	Total
Female	8	9	14	5	36
Male	14	20	14	3	51

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Escitalopram 20mg for 2 Weeks	Placebo (Sugar Pill)	Escitalopram 30mg for 8 Weeks	Escitalopram 20mg for 8 Weeks	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	1	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	4	4	4	1	13
White	17	24	24	7	72
More than one race	1	0	0	0	1
Unknown or Not Reported	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Escitalopram 20mg for 2 Weeks	Placebo (Sugar Pill)	Escitalopram 30mg for 8 Weeks	Escitalopram 20mg for 8 Weeks	Total
United States	22	29	28	8	87

Study locations

2 sites

Washington University
Saint Louis, Missouri 63110, United States
University of Pennsylvania
Philadelphia, Pennsylvania 19104, United States

References and documents

Publications

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. PubMed 32913021 ↗

Study documents

Protocol and statistical analysis plan · Oct 31, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 9, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02161458
Lead sponsor: University of Pennsylvania
Collaborators: Washington University School of Medicine
Responsible party: Sponsor
First posted: Jun 11, 2014
Start date: Jun 2014
Primary completion: Aug 2017
Completion: Jan 2019
Results posted: Mar 12, 2019
Last update: Apr 9, 2020

Study contacts

Yvette Sheline, M.D.

principal investigator · University of Pennsylvania

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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