Amyloid Beta ProteinPhase 4NCT02161458
Escitalopram Effects on CSF Amyloid Beta
A Phase 4 study testing Escitalopram 20mg for 2 weeks, Escitalopram 20mg for 8 weeks and Escitalopram 30mg for 8 weeks in people with Amyloid Beta Protein, run by University of Pennsylvania at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Amyloid Beta Protein
- What is being tested?
- Escitalopram 20mg for 2 weeks, Escitalopram 20mg for 8 weeks and Escitalopram 30mg for 8 weeks
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 98 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2014to Jan 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Washington University
St Louis, Missouri, 63110
About this study
Official title: Escitalopram Effects on CSF Amyloid Beta Total Concentrations
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
- Amyloid Beta Protein
- Being tested
- Escitalopram 20mg for 2 weeks, Escitalopram 20mg for 8 weeks, Escitalopram 30mg for 8 weeks, Placebo
- Keywords
- Escitalopram, Amyloid Beta, Cerebrospinal Fluid
- Medical subject headings
- Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Escitalopram 20mg for 2 weeksDrug
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 8 weeksDrug
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 30mg for 8 weeksDrug
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.
PlaceboDrug
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Escitalopram 20mg for 8 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 - 8 Weeks (we used week 8 minus baseline and week 2 minus baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2014 (estimated)
- Study startJun 2014
- Primary completionAug 2017
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyloid Beta ProteinStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Washington University School of Medicine
- Responsible party
- Sponsor
- Investigators
- Yvette Sheline, M.D., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02161458
- Sponsor's protocol ID
- R01AG041502
- Status last verified
- Apr 2020
- First submitted
- 5 Jun 2014
- Last updated
- 9 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
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 at a glance
From the registry record, last updated by the sponsor on 9 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Escitalopram Effects on CSF Amyloid Beta Total Concentrations
- ClinicalTrials.gov ID
- NCT02161458
- Acronym / sponsor ID
- R01AG041502
- Conditions
- Amyloid Beta Protein
- Keywords
- Escitalopram, Amyloid Beta, Cerebrospinal Fluid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Washington University School of Medicine
- Study start
- Jun 2014
- Primary completion
- Aug 2017 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 11 Jun 2014 (estimated)
- Results
- Posted 12 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Escitalopram 20mg for 2 weeks | Experimental | Drug: Escitalopram 20mg for 2 weeks30 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. |
| Placebo (sugar pill) | Placebo comparator | Drug: Placebo30 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. |
| Escitalopram 30mg for 8 weeks | Experimental | Drug: Escitalopram 30mg for 8 weeks30 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. |
| Escitalopram 20mg for 8 weeks | Experimental | Drug: Escitalopram 20mg for 8 weeks30 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. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Escitalopram 20mg for 2 weeks30 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 2 weeks |
| Escitalopram 20mg for 8 weeks30 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 20mg for 8 weeks |
| Escitalopram 30mg for 8 weeks30 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 | Escitalopram 30mg for 8 weeks |
| PlaceboAdditionally, 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. | Drug | Placebo (sugar pill) |
Primary outcome
Amyloid Beta Levels in CSF
Time frame: 2 - 8 Weeks (we used week 8 minus baseline and week 2 minus baseline)
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32913021Sheline 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yvette Sheline, M.D. principal investigator
University of Pennsylvania
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Escitalopram 20mg for 2 weeks, Escitalopram 20mg for 8 weeks and Escitalopram 30mg for 8 weeks in people with Amyloid Beta Protein, run by University of Pennsylvania at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amyloid Beta Levels in CSF (time frame: 2 - 8 Weeks (we used week 8 minus baseline and week 2 minus baseline)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02161458, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2020.