Protocol summary
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Study aim
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Evaluating the efficacy of agomelatine as add-on therapy on agitation/aggression and serum Brain-Derived Neurotrophic Factor (BDNF) levels of the patients with Alzheimer's disease.
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Design
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Placebo-controlled, parallel group, double blind, phase III randomised clinical trial on 52 patients
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Settings and conduct
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Neurology clinic of Imam Hossein academic hospital, Tehran, Iran
At first the caregivers will be asked to answer the Persian version of Cohen-Mansfield Agitation Inventory (CMAI) (visit 1, week 0), and then after six weeks. Blood samples will be collected at the baseline and final visit.
The investigators will be in touch with the patients’ caregivers weekly.
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Participants/Inclusion and exclusion criteria
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Inclusion criteria: Patients diagnosed with Alzheimer's disease (AD) who were ≥50 years, written consent obtained from the subject or the subject's legally authorized representative, suffering from aggression and/or agitation that developed after the onset of dementia, If female, must be of non-childbearing potential, or agree to use a clinically acceptable method of contraception.
Exclusion criteria: Unable to comply with the study visits, syndromes overlapping with AD, behavioral and psychological symptoms of dementia developed by other medical causes, recent alcohol or substance use disorder, current smoker, epilepsy, consumption of antipsychotics and/or melatonin during the past two weeks, patients with a disease of clinical significance or unstable conditions.
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Intervention groups
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Intervention: agomelatine with the initial dose of 6.25 mg daily for 2 days, then 12.5 mg daily for 3 days to reach the final dose of 25 mg daily for 37 days (end of week 6).
Control: a quarter of the placebo tablets daily for 2 days, a half for 3 days, and a whole placebo tablet daily for 37 days.
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Main outcome variables
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The Cohen-Mansfield Agitation Inventory (CMAI) score comparing with baseline
General information
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Reason for update
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Due to the possibility of non-cooperation of the patients, the research team decided to add 2 patients in each group and a block of 4 patients was added to the study.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20170608034390N10
Registration date:
2022-05-11, 1401/02/21
Registration timing:
prospective
Last update:
2024-06-13, 1403/03/24
Update count:
1
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Registration date
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2022-05-11, 1401/02/21
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2022-06-22, 1401/04/01
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Expected recruitment end date
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2023-03-21, 1402/01/01
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Evaluation of the Efficacy of Agomelatine as Add-on Therapy on the Aggression, Agitation, and its Relationship with Serum Brain-Derived Neurotrophic Factor (BDNF) of Patients with Alzheimer’s disease Dementia; A Double-blind, Randomized, Placebo-controlled Clinical Trial
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Public title
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Evaluation of the Efficacy of Agomelatine as Add-on Therapy on the Aggression, Agitation, and its Relationship with Serum Brain-Derived Neurotrophic Factor (BDNF) of Patients with Alzheimer’s disease Dementia
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Female and male patients 50 years of age and older
Being able to provide written informed consent or have written informed consent provided by a legally authorized representative (LAR) on behalf of the patient
Diagnosis of Alzheimer’s dementia (according to NINCDS-ADRDA) with a FAST score of 4 to 6 (inclusive)
Suffering from aggression and/or agitation that developed after the onset of dementia and must be severe enough to disrupt their functioning and occurred nearly daily or most of the days per week during the week prior to enrolment (or a score of > 39 on the Cohen-Mansfield Agitation Inventory)
If female must be of non-childbearing potential or must agree to use a clinically acceptable method of contraception or abstinence during the study.
Exclusion criteria:
The patient or caregiver is unable to comply with the study visits
Syndromes overlapping with Alzheimer’s dementia (vascular dementia is not an exclusion criterion)
Behavioral and psychological symptoms of dementia (BPSD) developed by other medical causes
Recent alcohol or substance abuse disorder
Current smokers
Secondary causes of Alzheimer’s disease (such as down syndrome)
Patients diagnosed with epilepsy
History of head trauma that had caused loss of consciousness
Patients diagnosed with Parkinson’s disease, frontotemporal dementia, Lewy body dementia, dementia following stroke
Diagnosis or history of psychotic disorders such as schizophrenia, schizoaffective disorder, delusional disorder, bipolar mood disorder)
Consumption of antipsychotics and/or melatonin during the past two weeks prior to screening
Concomitant strong CYP1A2 inhibitor medications consumption
Patients with a disease of clinical significance or unstable conditions (e.g., uncontrolled diabetes mellitus, uncontrolled hypertension, unstable pulmonary, renal, or hepatic disease, unstable ischemic heart disease, malignancy)
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Age
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From 50 years old
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Gender
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Both
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Phase
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3
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Groups that have been masked
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- Participant
- Care provider
- Investigator
- Outcome assessor
- Data analyser
- Data and Safety Monitoring Board
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Sample size
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Target sample size:
56
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Using the online software (www.sealedenvelope.com) and the block randomization method, will be utilized, and 14 blocks of four subjects will be used to randomize 56 patients.
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Blinding (investigator's opinion)
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Triple blinded
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Blinding description
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The participants, physicians, and the outcome assessors will be blinded to the assigned intervention using the specific generated random codes for each patient for data entry and analysis procedures. Agomelatine and placebo will be provided to the patients’ caregivers in opaque bottles, with both the placebo and agomelatine tablets having the same visual properties, both odorless and in yellow colors of the same size.
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Placebo
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Used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2022-03-15, 1400/12/24
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Ethics committee reference number
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IR.SBMU.PHARMACY.REC.1401.015
Health conditions studied
1
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Description of health condition studied
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Behavioral and Psychological Symptoms of Dementia
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ICD-10 code
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G30
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ICD-10 code description
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Alzheimer's disease
Primary outcomes
1
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Description
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Cohen-Mansfield Agitation Inventory (CMAI)
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Timepoint
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Weeks 0 and 6
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Method of measurement
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Persian version of CMAI
Secondary outcomes
1
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Description
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Level of serum Brain-derived neurotrophic factor (BDNF) from baseline
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Timepoint
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Weeks 0 and 6
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Method of measurement
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Blood sampling and specific BDNF kits
2
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Description
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Frequency of adverse drug reactions
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Timepoint
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Throughout the study
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Method of measurement
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Recording and evaluation of adverse events
Intervention groups
1
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Description
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Intervention group: agomelatine as add-on therapy, with the initial dose of 6.25 mg daily preferably in the afternoon for two days, which will be increased to 12.5 mg daily for three days to reach the final dose of 25 mg daily in the afternoon for 37 days (end of week six). The tablets can be administered without regard to meals.
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Category
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Treatment - Drugs
2
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Description
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Control group: The control group will receive placebo with the same pattern as add-on therapy, starting with a quarter of the placebo tablets daily preferably in the afternoon for two days, a half for three days, and a whole placebo tablet daily in the afternoon for 37 days (end of week six). The tablets can be administered without regard to meals.
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Category
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Placebo
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Shahid Beheshti University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Yes - There is a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Yes - There is a plan to make this available
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Data Dictionary
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Yes - There is a plan to make this available
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Title and more details about the data/document
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The results file will be uploaded in SPSS format to the UK Data Depository.
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When the data will become available and for how long
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At the end of the study and after data collection.
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To whom data/document is available
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For anyone interested.
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Under which criteria data/document could be used
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No need to send a request. The file will be uploaded to the online depository.
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From where data/document is obtainable
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To get the documents, refer to the UK Data Depository and download the relevant file.
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What processes are involved for a request to access data/document
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No need to send a request. The file will be uploaded to the depository.
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Comments
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