Alzheimer's DiseasePhase 2NCT00940589
Efficacy of Circadin® 2 mg in Patients With Mild to Moderate Alzheimer Disease Treated With AChE Inhibitor
A Phase 2 study testing Circadin in people with Alzheimer's Disease and Sleep Disorder, run by Neurim Pharmaceuticals Ltd. at 6 sites in 3 countries.
Trial summary
The aim of this exploratory randomized, placebo controlled study is to evaluate the efficacy of Circadin® 2mg in patients with mild to moderate Alzheimer Disease (AD) treated with the acetylcholinesterase (AChE) inhibitor. The effects of add-on Circadin® 2mg vs. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer's Disease, Sleep Disorder
- What is being tested?
- Circadin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 73 participants
- Where
- 6 sitesin 3 countries
- Study dates
- Sep 2009to May 2013
- Phase
- Phase 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent as dictated by local legal circumstances.
- Age range: adult patients between 50-85 years of age.
- Gender: men and women. Women of child bearing potential or within two years of the menopause must have a negative urine pregnancy test at the Screening Visit.
- A documented history of confirmed Alzheimer's disease
- Dementia severity: MMSE score > 15,
- Stable AChE inhibitor dose for 2 months prior to Screening visit.
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- Stable medications for non-excluded concurrent medical conditions for four weeks prior to the screening visit.
- Stable doses of B12 and/or Folic acid supplements for at least 3 months prior to enrollment and throughout the study.
- Cranial image: no evidence of focal disease to account for dementia (established by CT, PET or MRI). If there is no such available scan (CT, PET or MRI), one must be performed prior to enrollment.
- Health: Physically acceptable for the study with no pathology likely to occur during or immediately after the study, as confirmed by medical history and exam and ECG.
- Clinical laboratory values must be within normal limits, or judged not clinically significant by the investigator.
- Residence: Stable home situation with no planned move during the 28-week investigational period.
- A family member or a regular caregiver that will be available for visits and will ensure compliance. The caregiver must speak fluent Hebrew, Russian or English.
- Ability to ingest oral medication and participate in all scheduled evaluations.
- Ability to spend 2 daily hours outdoors exposed to sunlight.
Who cannot join
- Severe agitation.
- Unstable medical condition, mental retardation.
- moderate to severe depression as defined by DSM-IV
- Use of benzodiazepines or other hypnotics during the study and the preceding four weeks.
- Use of Circadin® during the two weeks prior to study enrollment.
- Pharmacological immunosuppression.
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- Participation in a clinical trial with any investigational agent within two months prior to study enrollment.
- Alcoholism.
- Known or suspected hypersensitivity to exogenous melatonin or melatonin receptor agonists.
- Patients with rare hereditary problems of galactose intolerance, the LAPP lactose deficiency or glucose mal absorption.
- Renal Failure with creatinine >150 micromol/l.
- Hepatic Failure with ASAT; ALAT; GGT levels above three times the upper normal limit.
- Clinically significant abnormal laboratory findings which have not been approved by the Safety Officer (sponsor)
- Other serious diseases that could interfere with patient assessment.
- Caregivers who are unwilling or unable to give informed consent or otherwise fulfill requirements of the study.
- Untreated B12 and/or Folic acid deficiency.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States4 sites
Meridien Research
Brooksville, Florida, 34601
Exodon LLC
Mount Arlington, New Jersey, 07856
Scranton Medical Institute
Scranton, Pennsylvania, 18503
Meridien Research
St. Petersburg, Florida, 33709
About this study
Official title: A Double-blind, Parallel Group, Randomized, Placebo Controlled Study of the Efficacy of Circadin® 2mg in Patients With Mild to Moderate Alzheimer Disease (AD) Treated With Acetylcholinesterase (AChE) Inhibitor
The aim of this exploratory randomized, placebo controlled study is to evaluate the efficacy of Circadin® 2mg in patients with mild to moderate Alzheimer Disease (AD) treated with the acetylcholinesterase (AChE) inhibitor. The effects of add-on Circadin® 2mg vs. placebo on the decline in cognitive skills and global functioning, as well as on daytime somnolence and will be assessed.
- Conditions
- Alzheimer's Disease, Sleep Disorder
- Being tested
- Circadin, Placebo
- Keywords
- Alzheimer's Disease, Acetylcholinesterase inhibitor, cognitive function, Circadin, Sleep disturbances
- Medical subject headings
- Alzheimer Disease, Sleep Wake Disorders, Parasomnias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CircadinDrug
Prolonged Release melatonin (Circadin) 2mg tablets
PlaceboDrug
Matched placebo tablets, with identical features to the Circadin tablets
| Study group | Role | What they receive |
|---|---|---|
| Circadin | Experimental | Drug Receives: Drug: Circadin |
| Placebo | Placebo comparator | drug Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to 24 Weeks in ADAS-cog
ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) is a cognitive testing instrument used in clinical trials. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention, and other cognitive abilities that are often referred to as the core symptoms of AD. The test comprises 11 items summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. A negative change indicates an improvement from baseline. ADAS-cog was measured at base line and at end of treatment after 24 weeks.
Measured: 24 weeks
Secondary outcomes (2)
Change From Baseline to 24 Weeks in iADL
Instrumental Activities of Daily Living (iADL). The scale rates activities that represent key life tasks that people need to manage. These tasks are valuable for evaluating persons with early-stage disease, both to assess the level of disease and to determine the person's ability to care for himself or herself. Scores of 0 or 1 are given to every task (Bathing, Dressing, Tolieting, transferring, Continence and Feeding) to a total score of 6. , while 0 represents a patient who is very dependent and 6 represents patient who is independent. iADL was measured at base line and at end of treatment after 24 weeks.
Measured: 24 weeks
Change From Baseline to 24 Weeks in MMSE
The Mini Mental State Examination (MMSE) is a brief assessment instrument used to assess cognitive function in elderly patients. The MMSE can be used to screen for cognitive impairment and as a measurement of cognition over time and with pharmacologic treatment. The instrument is divided into 2 sections. The first section measures orientation, memory, and attention: the maximum score is 21. The second section tests the ability of the patient to name objects, follow verbal and written commands, write a sentence, and copy figures: the maximum score is 9. The scoring range for the MMSE is 0-30. Higher score represents better performance. MMSE was measured at base line and at end of treatment after 24 weeks.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2009 (estimated)
- Study startSep 2009
- Primary completionFeb 2013
- Study completionMay 2013
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 (2)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurim Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00940589
- Sponsor's protocol ID
- NEU AZ1
- Status last verified
- May 2018
- First submitted
- 15 Jul 2009
- Last updated
- 1 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman-Marom A, Zisapel N. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014 Jun 18;9:947-61. doi: 10.2147/CIA.S65625. eCollection 2014.
PubMed 24971004McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2020 Nov 15;11(11):CD009178. doi: 10.1002/14651858.CD009178.pub4.
PubMed 33189083
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Parallel Group, Randomized, Placebo Controlled Study of the Efficacy of Circadin® 2mg in Patients With Mild to Moderate Alzheimer Disease (AD) Treated With Acetylcholinesterase (AChE) Inhibitor
- ClinicalTrials.gov ID
- NCT00940589
- Acronym / sponsor ID
- NEU AZ1
- Conditions
- Alzheimer's Disease, Sleep Disorder
- Keywords
- Alzheimer's Disease, Acetylcholinesterase inhibitor, cognitive function, Circadin, Sleep disturbances
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Neurim Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- Feb 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 16 Jul 2009 (estimated)
- Results
- Posted 1 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this exploratory randomized, placebo controlled study is to evaluate the efficacy of Circadin® 2mg in patients with mild to moderate Alzheimer Disease (AD) treated with the acetylcholinesterase (AChE) inhibitor. The effects of add-on Circadin® 2mg vs. placebo on the decline in cognitive skills and global functioning, as well as on daytime somnolence and will be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Circadin | Experimental | Drug: CircadinDrug |
| Placebo | Placebo comparator | Drug: Placebodrug |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Written informed consent as dictated by local legal circumstances.
- Age range: adult patients between 50-85 years of age.
- Gender: men and women. Women of child bearing potential or within two years of the menopause must have a negative urine pregnancy test at the Screening Visit.
- A documented history of confirmed Alzheimer's disease
- Dementia severity: MMSE score > 15,
Key exclusion criteria (16 listed)
- Severe agitation.
- Unstable medical condition, mental retardation.
- moderate to severe depression as defined by DSM-IV
- Use of benzodiazepines or other hypnotics during the study and the preceding four weeks.
- Use of Circadin® during the two weeks prior to study enrollment.
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 |
|---|---|---|
| CircadinProlonged Release melatonin (Circadin) 2mg tablets | Drug | Circadin |
| PlaceboMatched placebo tablets, with identical features to the Circadin tablets | Drug | Placebo |
Primary outcome
Change From Baseline to 24 Weeks in ADAS-cog
Time frame: 24 weeks
ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) is a cognitive testing instrument used in clinical trials. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention, and other cognitive abilities that are often referred to as the core symptoms of AD. The test comprises 11 items summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. A negative change indicates an improvement from baseline. ADAS-cog was measured at base line and at end of treatment after 24 weeks.
2 secondary outcomes
Change From Baseline to 24 Weeks in iADL
Time frame: 24 weeks
Change From Baseline to 24 Weeks in MMSE
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24971004Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman-Marom A, Zisapel N. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014 Jun 18;9:947-61. doi: 10.2147/CIA.S65625. eCollection 2014.
- Derived from this study: PubMed 33189083McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2020 Nov 15;11(11):CD009178. doi: 10.1002/14651858.CD009178.pub4.
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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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Circadin in people with Alzheimer's Disease and Sleep Disorder, run by Neurim Pharmaceuticals Ltd. at 6 sites in 3 countries.
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 15 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 1 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Israel, United Kingdom. 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 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 1 Jun 2018). 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 24 Weeks in ADAS-cog (time frame: 24 weeks). 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 NCT00940589, which also lists 2 linked publications.
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 1 Jun 2018.