Alzheimer's DiseasePhase 1NCT02061878
A Study to Evaluate the Effect of Bexarotene on Beta-Amyloid and Apolipoprotein E Metabolism in Healthy Subjects
A Phase 1 study testing Bexarotene in people with Alzheimer's Disease, run by ReXceptor, Inc. at 1 site in United States.
Trial summary
The primary objective of this proof of mechanism pilot clinical trial is to determine if the RXR agonist bexarotene acts in humans to alter the CSF levels of apoE and alter the clearance of Amyloid-Beta Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Bexarotene
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to Nov 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 21 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Young healthy adults (age 21-50)
- APOE3/3 genotype
Who cannot join
- Contraindications for blood or CSF sampling
- Bleeding disorder or taking anticoagulants/antiplatelets
- Chronic active infection
- Blood donation within the past month
- Active drug/alcohol dependence or abuse history with in the last 12 months
- Thyroid dysfunction
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- High triglycerides (>3.5 mmol/L)
- High cholesterol (>4.0 mmoL/L)
- Leukopenia, including low neutrophil count (<3 x 10^9/L)
- Neurological or psychiatric disorders
- Homeless or prisoner
- Pregnancy
- Incapable of self-informed consent
- Blood borne disease (HIV, Hepatitis)
- Actively smoking and incapable of using nicotine patches
- Known drug allergy to pain medication or local anesthetic
- Subjects that have participated in another study in the last 30 days
- Abnormalities in lumbar spine previously known within 12 months
- APOE2 or APOE4 allele
- Abnormal EKG
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Study to Evaluate the Effect of Bexarotene - an RXR Agonist - on Beta-Amyloid and Apolipoprotein E Metabolism in Healthy Subjects
The primary objective of this proof of mechanism pilot clinical trial is to determine if the RXR agonist bexarotene acts in humans to alter the CSF levels of apoE and alter the clearance of Amyloid-Beta
Read the detailed description
This is a double blinded, investigational drug study designed to measure the effect of bexarotene on the clearance of Aβ total and production of apoE in the human brain of young, healthy individuals with the APOE3/3 genotype. From the date of initial subject recruitment to the issuance of a final study report and closeout activities, the expected total study duration is 6 to 10 months.
Each participant will be screened for eligibility and randomized to receive either oral bexarotene or placebo control ("Test Article").The study has the potential to demonstrate the pharmacodynamic properties of a novel treatment approach to Alzheimer's disease. The primary biomarker measurements obtained from this study are believed to be highly dynamic and able to provide a rapid read-out of the biologic activity of the candidate therapeutic under study. In addition, exploratory analysis will involve a proteomics-based screen to identify proteins within both blood and CSF that are induced by the Test Article, thereby potentially identifying new biomarkers that can be used in future clinical trials to demonstrate bexarotene action and target engagement.
- Conditions
- Alzheimer's Disease
- Being tested
- Bexarotene, Placebo
- Keywords
- ApoE, beta-amyloid
- Medical subject headings
- Alzheimer Disease, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BexaroteneDrug
Also called Targretin®
Marketed product Targretin® soft gelatin capsule (75mg/capsule) is over-encapsulated in a size AA-el Swedish orange capsule. The subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days.
PlaceboDrug
Also called Avicel PH
The subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days.
| Study group | Role | What they receive |
|---|---|---|
| Bexarotene | Experimental | The subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days Receives: Drug: Bexarotene |
| Placebo | Placebo comparator | The subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the effect curve for newly generated beta-Amyloid (clearance phase),
Area under the effect curve from 21-48h for newly generated beta-Amyloid (clearance phase), which is computed for each individual as the area under the curve of the clearance portion of the labeled beta-Amyloid curve between 21 hour and 48 hours, normalized by plasma free leucine levels.
Measured: 21 - 48 hr
Secondary outcomes (1)
Fractional clearance rate of beta-Amyloid peptide in CNS
Fractional clearance rate (FCR) of beta-Amyloid peptide in CNS, computed for each individual as the slope of the natural logarithm of the clearance portion of the labeled beta-Amyloid curve between 21 hours and 36 hours 2) AUEC0-24 of apoE: Area under the effect curve from 0-24h for newly generated apoE (production phase) 3) Fractional synthesis rate (FSR) of apoE protein in CNS 4) Aβ and apoE concentrations: CSF beta-Amyloid and apoE concentrations for each time point 5)Size of apoE-containing high density lipoprotein particles in CSF as assessed by native PAGE 6) Labeled/Unlabeled Leu ratio (% of 13C6 Leu) in plasma and CSF for 48 hours following start of 13C6 Leu administration 7) Bexarotene concentrations in blood and CSF 8) Plasma beta-Amyloid total and apoE concentrations at baseline compared to final plasma beta-Amyloid total and apoE concentrations
Measured: 21 - 36 hrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2014 (estimated)
- Study startAug 2014
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- 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 1
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- ReXceptor, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Craig T Curtis, MD, Principal investigator, Compass Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02061878
- Sponsor's protocol ID
- REXCEPTOR-101
- Status last verified
- Aug 2015
- First submitted
- 5 Feb 2014
- Last updated
- 13 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Ghosal K, Haag M, Verghese PB, West T, Veenstra T, Braunstein JB, Bateman RJ, Holtzman DM, Landreth GE. A randomized controlled study to evaluate the effect of bexarotene on amyloid-beta and apolipoprotein E metabolism in healthy subjects. Alzheimers Dement (N Y). 2016 Jun 17;2(2):110-120. doi: 10.1016/j.trci.2016.06.001. eCollection 2016 Jun.
PubMed 29067298
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Study to Evaluate the Effect of Bexarotene - an RXR Agonist - on Beta-Amyloid and Apolipoprotein E Metabolism in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02061878
- Acronym / sponsor ID
- REXCEPTOR-101
- Conditions
- Alzheimer's Disease
- Keywords
- ApoE, beta-amyloid
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- ReXceptor, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2014
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 13 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this proof of mechanism pilot clinical trial is to determine if the RXR agonist bexarotene acts in humans to alter the CSF levels of apoE and alter the clearance of Amyloid-Beta
Detailed description
This is a double blinded, investigational drug study designed to measure the effect of bexarotene on the clearance of Aβ total and production of apoE in the human brain of young, healthy individuals with the APOE3/3 genotype. From the date of initial subject recruitment to the issuance of a final study report and closeout activities, the expected total study duration is 6 to 10 months.
Each participant will be screened for eligibility and randomized to receive either oral bexarotene or placebo control ("Test Article").The study has the potential to demonstrate the pharmacodynamic properties of a novel treatment approach to Alzheimer's disease. The primary biomarker measurements obtained from this study are believed to be highly dynamic and able to provide a rapid read-out of the biologic activity of the candidate therapeutic under study. In addition, exploratory analysis will involve a proteomics-based screen to identify proteins within both blood and CSF that are induced by the Test Article, thereby potentially identifying new biomarkers that can be used in future clinical trials to demonstrate bexarotene action and target engagement.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bexarotene | Experimental | Drug: BexaroteneThe subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days |
| Placebo | Placebo comparator | Drug: PlaceboThe subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days. |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Young healthy adults (age 21-50)
- APOE3/3 genotype
Key exclusion criteria (20 listed)
- Contraindications for blood or CSF sampling
- Bleeding disorder or taking anticoagulants/antiplatelets
- Chronic active infection
- Blood donation within the past month
- Active drug/alcohol dependence or abuse history with in the last 12 months
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 |
|---|---|---|
| BexaroteneAlso: Targretin®Marketed product Targretin® soft gelatin capsule (75mg/capsule) is over-encapsulated in a size AA-el Swedish orange capsule. The subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days. | Drug | Bexarotene |
| PlaceboAlso: Avicel PHThe subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days. | Drug | Placebo |
Primary outcome
Area under the effect curve for newly generated beta-Amyloid (clearance phase),
Time frame: 21 - 48 hr
Area under the effect curve from 21-48h for newly generated beta-Amyloid (clearance phase), which is computed for each individual as the area under the curve of the clearance portion of the labeled beta-Amyloid curve between 21 hour and 48 hours, normalized by plasma free leucine levels.
1 secondary outcome
Fractional clearance rate of beta-Amyloid peptide in CNS
Time frame: 21 - 36 hrs
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2015.
- Derived from this study: PubMed 29067298Ghosal K, Haag M, Verghese PB, West T, Veenstra T, Braunstein JB, Bateman RJ, Holtzman DM, Landreth GE. A randomized controlled study to evaluate the effect of bexarotene on amyloid-beta and apolipoprotein E metabolism in healthy subjects. Alzheimers Dement (N Y). 2016 Jun 17;2(2):110-120. doi: 10.1016/j.trci.2016.06.001. eCollection 2016 Jun.
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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.
Craig T Curtis, MD principal investigator
Compass Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bexarotene in people with Alzheimer's Disease, run by ReXceptor, Inc. at 1 site 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 2 inclusion and 20 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 13 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Area under the effect curve for newly generated beta-Amyloid (clearance phase), (time frame: 21 - 48 hr). 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 NCT02061878, 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 13 Aug 2015.