Escitalopram Effects on CSF Amyloid Beta

• ClinicalTrials.gov Identifier: NCT02161458
• Recruitment Status: Active, not recruiting
• First Posted: June 11, 2014
• Results First Posted: March 12, 2019
• Last Update Posted: March 12, 2019
• Sponsor: University of Pennsylvania
• Collaborator: Washington University School of Medicine
• Information provided by (Responsible Party): University of Pennsylvania

Tracking Information

• First Submitted Date: June 5, 2014
• First Posted Date: June 11, 2014
• Results First Submitted Date: November 20, 2018
• Results First Posted Date: March 12, 2019
• Last Update Posted Date: March 12, 2019
• Study Start Date: June 2014
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 19, 2019)

Amyloid Beta Levels in CSF [ Time Frame: 2 - 8 Weeks ]

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.

Original Primary Outcome Measures (submitted: June 10, 2014)

Amyloid Beta Levels in CSF [ Time Frame: Two Weeks ]

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 2 weeks of exposure with escitalopram.

• Change History: Complete list of historical versions of study NCT02161458 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Escitalopram Effects on CSF Amyloid Beta
• Official Title: Escitalopram Effects on CSF Amyloid Beta Total Concentrations
• 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:

1. Screening Visit: Consent and screening procedures will be complete. Participants will be randomized 1:1 to receive escitalopram or placebo.
2. 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.
3. 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:

1. Screening Visit: Consent and screening procedures will be complete. Participants will be randomized 1:1 to receive escitalopram or placebo.
2. 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.
3. Study Visit 2: Researchers will check in with participants and participants will receive another 4 weeks of study medication.
4. 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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Health Services Research
• Condition: Amyloid Beta Protein

Intervention

• Drug: Escitalopram 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.
• Drug: Escitalopram 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.
• Drug: Escitalopram 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.
• Drug: Placebo
  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.

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.
  Intervention: 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.
  Intervention: 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.
  Intervention: 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.
  Intervention: Drug: Escitalopram 20mg for 8 weeks

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 19, 2019): 98
• Original Estimated Enrollment (submitted: June 10, 2014): 60
• Estimated Study Completion Date: August 2019
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02161458
• Other Study ID Numbers: R01AG041502( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of Pennsylvania
• Study Sponsor: University of Pennsylvania
• Collaborators: Washington University School of Medicine

Investigators

• Principal Investigator: Yvette Sheline, M.D.; University of Pennsylvania

• PRS Account: University of Pennsylvania
• Verification Date: February 2019