Alzheimer's DiseasePhase 1/2NCT01560585
Open Label Study of Isotretinoin in Mild to Moderate Alzheimer's Disease
A Phase 1/2 study testing Isotretinoin in people with Alzheimer's Disease, run by University Hospitals Cleveland Medical Center at 1 site in United States.
Trial summary
This is an open label study of isotretinoin, a medication which is FDA approved for treatment of other conditions to determine initial safety in Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Isotretinoin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to Aug 2014
- Phase
- Phase 1/2
- 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 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Probable AD by DSM IV and NINCDS-ADRDA criteria
- Females must be surgically sterile (bilateral tubal ligation, both ovaries removed or hysterectomy) or post-menopausal for at least 2 years.
- > 50 years of age
- Residing in the community at baseline (includes assisted living facilities, long-term care nursing facilities)
- Mini Mental State Examination at screen of 12-26 (inclusive)
- No medical contraindications to study participation
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- Fluent in English at least 8 years of education.
- Supervision available for study medication. Caregiver/study partner to accompany participant to all visits. Study partner must have direct contact with the participant > 2 days/week
- Able to ingest oral medication.
- Neuroimaging (CT or MRI or PET) consistent with the diagnosis of AD at some time after the onset of the memory decline.
- Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator
- Stable use of cholinesterase inhibitors and memantine is permitted if doses are stable for 3 months prior to enrollment. Dose should be stable throughout the study unless it is clinically necessary to adjust the medication.
- Stable use of anti-depressants is permitted if doses are stable for 3 months prior to enrollment. Dose should be stable throughout the study unless it is clinically necessary to adjust the medication.
Who cannot join
- Dementia not due to probable Alzheimer's disease
- Pregnancy, breastfeeding. The rationale is that retinoids are teratogenic and are excreted in breast milk.
- History of clinically significant stroke
- Modified Hachinski Ischemia score ≥ 4
- Current evidence or history in past two years of epilepsy, seizure, focal brain lesion, head injury with loss of consciousness or DSM IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, severe alcohol or substance abuse.
- Sensory impairment which would prevent subject from participating in or cooperating with the protocol.
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- Use of another investigational agent within two months.
- Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational new drug including clinically significant or unstable hematologic, hepatic, cardiovascular (including history of ventricular fibrillation or ventricular tachycardia), pulmonary, gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratory abnormality. Abnormal liver function test, including AST, ALT, total bilirubin, or prothrombin time. The rationale is that retinoids can be hepatotoxic.
- Participants receiving behavioral medications (including antidepressants, antipsychotics and anxiolytics) must be on stable doses for at least 4 weeks prior to randomization.
- Active neoplastic disease and any medical conditions requiring concurrent immunosuppression.
- Hypertriglyceridemia greater than 500 mg/dL despite statin/fibrate therapy. The rationale is that retinoids can increase lipids, particularly triglyceride and this can lead to pancreatitis.
- Any medical conditions requiring concurrent use of tetracycline, minocycline, or doxycycline. The rationale is due to enhanced risk of increased intracranial pressure.
- Hypersensitivity to retinoids.
- Presence of psychosis or hallucinations at baseline as determined by Neuropsychiatric inventory or Geriatric Depression Scale-short form greater than or equal to five
- Presence of any unstable cardiovascular disease, uncontrolled diabetes, chronic inflammatory or infectious conditions. Retinoids have been associated with chest pain of unclear etiology, increased serum glucose, myelosuppression and increased risk of infection.
- Use of Drugs and supplements such as: Vitamin A supplements beyond 100% RDA, other immunosuppressants (corticosteroids, chemotherapeutic agents, etc.), Warfarin , Fish Oil (DHA)
- Any other disease or medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this clinical trial.
Trial locations and contacts
1 site in 1 country.
About this study
This is an open label study of isotretinoin, a medication which is FDA approved for treatment of other conditions to determine initial safety in Alzheimer's disease.
Read the detailed description
Retinoids have some relevant characteristics that could be considered useful in treating AlZheimer's disease. These include anti-inflammatory properties, possible anti-amyloid formation proeprties and inhibition of cell cycle properties
- Conditions
- Alzheimer's Disease
- Being tested
- Isotretinoin
- Keywords
- Isotretinoin, Alzheimer's disease, Dementia, Retinoid
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsotretinoinDrug
Isotretinoin 0.5 mg per kilogram body weight (rounded to nearest 10 mg) per day for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Open label | Experimental | All participants will receive Isotretinoin for 24 weeks Receives: Drug: Isotretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Six Month Timepoint in the Score on the Alzheimer's Disease Assessment Scale- Cognitive Subscale
Alzheimer's disease Assessment Scale- Cognitive subscale is a scale to measure cognitive function used in dementia clinical trials. No primary outcome data since study was terminated before any participaant completed
Measured: 6 months from baseline
Secondary outcomes (1)
Number of Adverse Effects
Any adverse events reported by subject or study partner will be recorded at each visit after screening (Baseline, and visits at week 4, 8, 12, 16, 20, 24, and 28 (four weeks after treatment discontinuation).
Measured: 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2012 (estimated)
- Study startApr 2012
- Primary completionAug 2014
- Study completionAug 2014
Why it stopped: Adverse events in 2/3 participants; study was halted but not restarted after this due to insufficnet funds as well
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 Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospitals Cleveland Medical CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alan Lerner, MD, University Hospitals Cleveland Medical Center
- Investigators
- Alan J Lerner, MD, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01560585
- Sponsor's protocol ID
- ISOTRT-01
- Status last verified
- May 2022
- First submitted
- 15 Mar 2012
- Last updated
- 15 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Not anticipated to release subject level data
Publications
Lee HP, Casadesus G, Zhu X, Lee HG, Perry G, Smith MA, Gustaw-Rothenberg K, Lerner A. All-trans retinoic acid as a novel therapeutic strategy for Alzheimer's disease. Expert Rev Neurother. 2009 Nov;9(11):1615-21. doi: 10.1586/ern.09.86.
PubMed 19903021
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Study of Isotretinoin in Mild to Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT01560585
- Acronym / sponsor ID
- ISOTRT-01
- Conditions
- Alzheimer's Disease
- Keywords
- Isotretinoin, Alzheimer's disease, Dementia, Retinoid
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Adverse events in 2/3 participants; study was halted but not restarted after this due to insufficnet funds as well
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Study start
- Apr 2012 (actual)
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 22 Mar 2012 (estimated)
- Results
- Posted 15 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label study of isotretinoin, a medication which is FDA approved for treatment of other conditions to determine initial safety in Alzheimer's disease.
Detailed description
Retinoids have some relevant characteristics that could be considered useful in treating AlZheimer's disease. These include anti-inflammatory properties, possible anti-amyloid formation proeprties and inhibition of cell cycle properties
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open label | Experimental | Drug: IsotretinoinAll participants will receive Isotretinoin for 24 weeks |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Probable AD by DSM IV and NINCDS-ADRDA criteria
- Females must be surgically sterile (bilateral tubal ligation, both ovaries removed or hysterectomy) or post-menopausal for at least 2 years.
- > 50 years of age
- Residing in the community at baseline (includes assisted living facilities, long-term care nursing facilities)
- Mini Mental State Examination at screen of 12-26 (inclusive)
Key exclusion criteria (17 listed)
- Dementia not due to probable Alzheimer's disease
- Pregnancy, breastfeeding. The rationale is that retinoids are teratogenic and are excreted in breast milk.
- History of clinically significant stroke
- Modified Hachinski Ischemia score ≥ 4
- Current evidence or history in past two years of epilepsy, seizure, focal brain lesion, head injury with loss of consciousness or DSM IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, severe alcohol or substance abuse.
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 |
|---|---|---|
| IsotretinoinIsotretinoin 0.5 mg per kilogram body weight (rounded to nearest 10 mg) per day for 24 weeks | Drug | Open label |
Primary outcome
Change From Baseline to Six Month Timepoint in the Score on the Alzheimer's Disease Assessment Scale- Cognitive Subscale
Time frame: 6 months from baseline
Alzheimer's disease Assessment Scale- Cognitive subscale is a scale to measure cognitive function used in dementia clinical trials. No primary outcome data since study was terminated before any participaant completed
1 secondary outcome
Number of Adverse Effects
Time frame: 28 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19903021Lee HP, Casadesus G, Zhu X, Lee HG, Perry G, Smith MA, Gustaw-Rothenberg K, Lerner A. All-trans retinoic acid as a novel therapeutic strategy for Alzheimer's disease. Expert Rev Neurother. 2009 Nov;9(11):1615-21. doi: 10.1586/ern.09.86.
- University Hospitals Case Medical CenterLink provided by the sponsor.
- Individual participant dataSharing planned: No. Not anticipated to release subject level data
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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.
Alan J Lerner, MD principal investigator
University Hospitals Cleveland Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Isotretinoin in people with Alzheimer's Disease, run by University Hospitals Cleveland Medical Center 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 13 inclusion and 17 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: stopped early, as of the sponsor's last update on 15 Jun 2022. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 15 Jun 2022). 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?
Change From Baseline to Six Month Timepoint in the Score on the Alzheimer's Disease Assessment Scale- Cognitive Subscale (time frame: 6 months from 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 NCT01560585, 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 15 Jun 2022.