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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-002707-10 | EudraCT Number |
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| Name | Class |
|---|---|
| Filadelfia Epilepsy Hospital | OTHER |
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The main objective of the MONANTI study is twofold:
Firstly, to determine the serum concentration (SC) the anti-dementia drugs donepezil and memantine in a broadly defined clinical population of patients suffering from dementia treated with the two drugs in question. Secondly, to determine whether adjustment of treatment of anti-dementia medication based on measurements of the SC will benefit patients in terms of cognitive performance, activities of daily living (ADL), frequency and severity of side effects.
The reason for conduction of this study is that the relationship between serum-level of anti-dementia drugs, clinical efficacy, compliance and side effects has only been scarcely investigated.
Both a previously published study and a preliminary (pilot)study conducted imply that roughly 50 % of patients on donepezil have SC outside the recommended therapeutic reference range (TRR).
Thus, MONANTI will investigate if this is indeed the case in a broadly comprised population of patients with dementia treated with donepezil or memantine. In addition, MONANTI will link SC to co-morbidity, level of compliance, medication interactions. It is hypothesized that the efficacy of anti-dementia drugs can be significantly improved by adjustment of treatment according to SC. Also, it is hypothesized that the burden of side effects can be reduced in patients in whom too high SC are detected, if dose reduction or change of treatment drug is done.
MONANTI is a randomized study, in which the assessor is blinded to avoid related biases to the extent possible.
To meet the enrollment criteria eligible participants must:
A) be newly diagnosed with either Alzheimer's disease dementia, dementia with Lewy-bodies or Parkinson's disease with dementia and B) be scheduled for treatment with either donepezil or memantine. C) not meet a list of (exclusion) criteria, which have been set up in order to avoid blur and biases of the results.
D) be able to give written informed consent to participation in presence of a close relative.
After enrollment the participants will be randomly assigned to one of two study groups. In the first of these, the control group, the participants receive standard treatment and follow-up at the outpatient clinic. In addition, all participants in the control group who complete the trial will have a blood sample collected at the final visit to measure the SC of the anti-dementia drug along with a genetic test for a few key genes thought to be relevant for the study (two liver enzymes (cyp2D6, cyp3A4/5, APOE-genotype, butyrylcholine-esterase K-variant).
In the other group, the intervention group, the participators will be closely monitored for side effects after prescription of anti-dementia drugs. All participants in the intervention group will be offered a measurement of the SC in case they experience drug side effects within 2 months of treatment initiation. All participants in the intervention group will have a measurement of the SC done at the 6 months visit. The measured SC will be compared to the TRR of the drug in question. This information, along with details from the clinical assessment at the 6 month visit will be used to guide the decision of whether or not to adjust treatment. All decisions on treatment adjustment during the trial are done by the PI according to details in the protocol.
All participants in the intervention group are evaluated again at a 12 month visit, identical to that of the control groups.
To assess the possible effects of SC guided treatment adjustment six clinical tests/rating scales will be used (MMSE, ACE, NPI-Q, DAD, CGI, GDS). The tests/rating scales will be administered both at the enrollement visit and one year later at the final 12 month follow-up visit.
To measure the effect of donepezil on brain cholinergic function approx. 30 participants will be recruited for electroencephalography (EEG). These participants will have an EEG done at enrollment and after 12 months.
In addition to the above mentioned quantitative study a qualitative study with relatives of enrolled participants is planned.
All the needed approvals have been obtained according to Danish law (approval by the Danish Data Protection Agency, Scientific Ethics Committee for Region Sjaelland, The Danish Medical Agencies).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of care | Active Comparator | Participants allocated to this arm follow the usual routines of the out patient dementia clinic but are requested to have the serum level of the prescribed drug measured after 12 month. Also, CYP2D6, BcHE K and APOe4 status will be determined after 12 months. |
|
| Intervention arm | Experimental | Participants allocated to this arm follow are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention arm not experiencing side effects will have their treatment adjusted after 6 months based upon serum level of the drug in question. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Donepezil | Drug | Adjustment of treatment with donepezil according to serum level. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change of Mini Mental State Examination (MMSE) Test Result | Widely used clinical test for brief assesment of cognitive function. Total score ranging from 0 (worst) to 30 (best). | 1 year (enrollment in study and at 1-year follow-up) |
| Change of Adenbrooke's Cognitive Examination (ACE) Test Result | Widely used clinical test for assesment of cognitive function. The total score ranges from 0 (worst) 100 (best) and includes the score of the MMSE test (0-30). | 1 year (enrollment in study and at 1-year follow-up) |
| Percentage of Participants With a Serum Concentration Within the Therapeutic Reference Range (TRR) at 12 Month Follow-up Visit. | Percentage of participans in each group with serum concentrations of the study drugs within the therapeutic reference range (TRR) at the 12 month follow-up visit. According to the 2017 AGNP consensus guidelines the TRRs are "ranges of drug concentrations in blood that specify a lower limit below which a drug induced therapeutic response is relatively unlikely to occur and an upper limit above which tolerability decreases or above which it is relatively unlikely that therapeutic improvement may be still enhanced" (Pharmacopsychiatry . 2018 Jan;51(1-02):9-62. doi: 10.1055/s-0043-116492. Epub 2017 Sep 14). Donepezil has a serum TRR of 50-75 nanograms per milliliter (ng/mL) and memantine has a serum TRR of 90-150 ng/mL. | Counted at the 12 month visit |
| Level of Compliance to Treatment | The level to which the medication has been ingested as prescribed. Both the participant him/her self is questioned as is the primary relative. The level of compliance is rated as belonging to one of the four categories: 1) 'completely regular drug intake' (no missed daily doses within 6 months), 2 'regular drug intake' (less than 10 missed daily doses within 6 months), 3) 'less regular drug intake' (10 - 30 missed daily doses with 6 months), 4) 'irregular drug intake' (more than 30 missed daily doses within 6 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Change of Clinical Global Impression (CGI) Score Result | The overall clinical impression of the clinical response to treatment as assessed by the investigator. Ranges from 1 (very much improved) to 7 (very much worse). | 1 year (enrollment in study and at 1-year follow-up) |
| Change in Geriatric Depression Scale (GDS) Symptoms Score |
| Measure | Description | Time Frame |
|---|---|---|
| Genetic Test for APOe4 Allele Status. | The APOe4 allele is linked to an increased risk of developing Alzheimer's disease. | For participants who complete the trial APOe4 allele status is assessed at the 1 year visit. |
Inclusion Criteria:
The following 3 inclusion criteria (A+B+C) must be met:
A. Participant must be newly diagnosed with one of the three conditions below
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter Høgh, MD, ph.d. | Regionalt Videnscenter for Demens | Principal Investigator |
| Michael Fischer, MD | Regionalt Videnscenter for Demens | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Regionalt Videnscenter for Demens | Roskilde | Region Sjælland | 4000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40034344 | Derived | Fischer MHF, Zibrandtsen IC, Johannsen P, Siersma V, Rasmussen JB, Larsen JB, Hogh P. Therapeutic drug monitoring for dose optimization in Alzheimer's disease and in dementia with Lewy bodies: A randomized single-blinded clinical trial. J Alzheimers Dis Rep. 2024 Nov 24;8(1):1516-1528. doi: 10.1177/25424823241289373. eCollection 2024. |
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A total of 132 participants recruited because a total of 110 participants assessable at the 6 month visit were needed.
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard of Care | Participants allocated to this arm follow the usual routines of the out patient dementia clinic but are requested to have the serum level of the prescribed drug measured after 12 month. Also, CYP2D6, BcHE K and APOe4 status will be determined after 12 months. Measurement of serum level of anti-dementia drug: Participants allocated to the intervention arm are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention group not experiencing side effects will have their treatment adjusted after 6 months based upon serum levels of the drug in question. Participants allocated to the standard of care arm follow the usual routines of the dementia clinic but are requested to have the serum level of the prescribed drug and CYP2D6-genotype measured after 12 month. |
| FG001 | Intervention Arm | Participants allocated to this arm follow are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention arm not experiencing side effects will have their treatment adjusted after 6 months based upon serum level of the drug in question. Donepezil: Adjustment of treatment with donepezil according to serum level. Memantine: Adjustment of treatment with memantine according to serum level. Measurement of serum level of anti-dementia drug: Participants allocated to the intervention arm are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention group not experiencing side effects will have their treatment adjusted after 6 months based upon serum levels of the drug in question. Participants allocated to the standard of care arm follow the usual routines of the dementia clinic but are requested to have the serum level of the prescribed drug and CYP2D6-genotype measured after 12 month. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard of Care | Participants allocated to this arm follow the usual routines of the out patient dementia clinic but are requested to have the serum level of the prescribed drug measured after 12 month. Also, CYP2D6, BcHE K and APOe4 status will be determined after 12 months. Measurement of serum level of anti-dementia drug: Participants allocated to the intervention arm are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention group not experiencing side effects will have their treatment adjusted after 6 months based upon serum levels of the drug in question. Participants allocated to the standard of care arm follow the usual routines of the dementia clinic but are requested to have the serum level of the prescribed drug and CYP2D6-genotype measured after 12 month. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change of Mini Mental State Examination (MMSE) Test Result | Widely used clinical test for brief assesment of cognitive function. Total score ranging from 0 (worst) to 30 (best). | Posted | Mean | Standard Deviation | difference in MMSE units on a scale | 1 year (enrollment in study and at 1-year follow-up) |
|
Adverse event data were collected for each participant from the date of enrollment until the day of completion, ie. approximately 1 year.
Details on all adverse events were collected and recorded according to the ICH E6 (R2) GCP guidelines. The primary investigator assessed whether an adverse event was classified as serious (Serious Adverse Event, SAE) or non-serious (non-serious adverse event, AE) and whether the event was related to the study drugs or not. Details on non-related SAEs and AEs were con not collected and reported according to prespecified criteria, instead a detailed description was given in the case report file.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard of Care | Participants allocated to this arm follow the usual routines of the out patient dementia clinic but are requested to have the serum level of the prescribed drug measured after 12 month. Also, CYP2D6, BcHE K and APOe4 status will be determined after 12 months. Measurement of serum level of anti-dementia drug: Participants allocated to the intervention arm are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention group not experiencing side effects will have their treatment adjusted after 6 months based upon serum levels of the drug in question. Participants allocated to the standard of care arm follow the usual routines of the dementia clinic but are requested to have the serum level of the prescribed drug and CYP2D6-genotype measured after 12 month. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| various minor non-related events | General disorders | Systematic Assessment | various minor non-related events not meeting the criteria for SAE. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Fischer | Department of Neurology, Zealand University Hospital | +4547322800 | mihh@regionsjaelland.dk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 19, 2022 | Mar 28, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 12, 2019 | Feb 2, 2025 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D003704 | Dementia |
| D020961 | Lewy Body Disease |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
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| ID | Term |
|---|---|
| D000077265 | Donepezil |
| D008559 | Memantine |
| ID | Term |
|---|---|
| D007189 | Indans |
| D007192 | Indenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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Single blinded, randomized study with two arms: 'standard of care' arm and 'intervention' arm. Participants in the intervention arm will have their treatment adjusted according to Serum levels of the anti-dementia drug prescribed.
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| Memantine |
| Drug |
Adjustment of treatment with memantine according to serum level. |
|
| Measurement of serum level of anti-dementia drug | Diagnostic Test | Participants allocated to the intervention arm are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention group not experiencing side effects will have their treatment adjusted after 6 months based upon serum levels of the drug in question. Participants allocated to the standard of care arm follow the usual routines of the dementia clinic but are requested to have the serum level of the prescribed drug and CYP2D6-genotype measured after 12 month. |
|
| Level of compliance will be scored at the one year follow-up by both questioning the participant and the primary relative. |
The Geriatric Depression Scale (GDS) is a questionaire administered by the investigator to the participant. GDS is used to assess symptoms of depression in the elderly. A 15 item version of the GDS is used with a score from 0 (best) to 15 (worst). |
| The GDS is administered to all participants at the both the baseline and 12-month follow-up visit. |
| Change of Disability Assessment for Dementia (DAD) Score Result | A questionaire filled in by the primary relative of the participant. DAD measures the impact of dementia symptoms on activities of daily living (ADL), including eating, dressing, personal hygiene. Total score ranges from 0 (worst) to 40 (best) | 1 year (enrollment in study and at 1-year follow-up) |
| Change of Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Result | A questionaire filled in by the primary relative of the participant. NPI-Q measures the severity of neuropsychiatric symptoms of demented patients. The total score ranges between 0 (best) and (36 worst). | 1 year (enrollment in study and at 1-year follow-up) |
| C2D6 Phenotype | Cyp2D6 is the gene which expresses the enzyme CYP2D6. Donepezil is metabolized by CYP2D6. | For participants in the standard of care arm CYP2D6 status will be determined 1 year after enrollment. For participants in the intervention arm Cyp2D6 will be tested within 2 months if side effects are experienced, if not then after 6 months. |
| Genetic Test for BcHE K Variant | BcHE butyryl cholinesterase (BChE), K variant. | For participants in the standard of care arm BcHE K variant status will be tested 1 year after enrollment. For participants in the intervention arm BcHE K variant status will be determined at the 6 month follow-up. |
| BG001 | Intervention Arm | Participants allocated to this arm follow are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention arm not experiencing side effects will have their treatment adjusted after 6 months based upon serum level of the drug in question. Donepezil: Adjustment of treatment with donepezil according to serum level. Memantine: Adjustment of treatment with memantine according to serum level. Measurement of serum level of anti-dementia drug: Participants allocated to the intervention arm are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention group not experiencing side effects will have their treatment adjusted after 6 months based upon serum levels of the drug in question. Participants allocated to the standard of care arm follow the usual routines of the dementia clinic but are requested to have the serum level of the prescribed drug and CYP2D6-genotype measured after 12 month. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Intervention Arm | Participants allocated to this arm follow are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention arm not experiencing side effects will have their treatment adjusted after 6 months based upon serum level of the drug in question. Donepezil: Adjustment of treatment with donepezil according to serum level. Memantine: Adjustment of treatment with memantine according to serum level. Measurement of serum level of anti-dementia drug: Participants allocated to the intervention arm are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention group not experiencing side effects will have their treatment adjusted after 6 months based upon serum levels of the drug in question. Participants allocated to the standard of care arm follow the usual routines of the dementia clinic but are requested to have the serum level of the prescribed drug and CYP2D6-genotype measured after 12 month. |
|
|
| Primary | Change of Adenbrooke's Cognitive Examination (ACE) Test Result | Widely used clinical test for assesment of cognitive function. The total score ranges from 0 (worst) 100 (best) and includes the score of the MMSE test (0-30). | Posted | Mean | Standard Deviation | difference in ACE units on a scale | 1 year (enrollment in study and at 1-year follow-up) |
|
|
|
| Primary | Percentage of Participants With a Serum Concentration Within the Therapeutic Reference Range (TRR) at 12 Month Follow-up Visit. | Percentage of participans in each group with serum concentrations of the study drugs within the therapeutic reference range (TRR) at the 12 month follow-up visit. According to the 2017 AGNP consensus guidelines the TRRs are "ranges of drug concentrations in blood that specify a lower limit below which a drug induced therapeutic response is relatively unlikely to occur and an upper limit above which tolerability decreases or above which it is relatively unlikely that therapeutic improvement may be still enhanced" (Pharmacopsychiatry . 2018 Jan;51(1-02):9-62. doi: 10.1055/s-0043-116492. Epub 2017 Sep 14). Donepezil has a serum TRR of 50-75 nanograms per milliliter (ng/mL) and memantine has a serum TRR of 90-150 ng/mL. | Posted | Count of Participants | Participants | Counted at the 12 month visit |
|
|
|
| Primary | Level of Compliance to Treatment | The level to which the medication has been ingested as prescribed. Both the participant him/her self is questioned as is the primary relative. The level of compliance is rated as belonging to one of the four categories: 1) 'completely regular drug intake' (no missed daily doses within 6 months), 2 'regular drug intake' (less than 10 missed daily doses within 6 months), 3) 'less regular drug intake' (10 - 30 missed daily doses with 6 months), 4) 'irregular drug intake' (more than 30 missed daily doses within 6 months) | Posted | Count of Participants | Participants | Level of compliance will be scored at the one year follow-up by both questioning the participant and the primary relative. |
|
|
|
| Secondary | Change of Clinical Global Impression (CGI) Score Result | The overall clinical impression of the clinical response to treatment as assessed by the investigator. Ranges from 1 (very much improved) to 7 (very much worse). | Posted | Mean | Standard Deviation | score on a scale | 1 year (enrollment in study and at 1-year follow-up) |
|
|
|
| Secondary | Change in Geriatric Depression Scale (GDS) Symptoms Score | The Geriatric Depression Scale (GDS) is a questionaire administered by the investigator to the participant. GDS is used to assess symptoms of depression in the elderly. A 15 item version of the GDS is used with a score from 0 (best) to 15 (worst). | Posted | Mean | Standard Deviation | units on a scale | The GDS is administered to all participants at the both the baseline and 12-month follow-up visit. |
|
|
|
| Secondary | Change of Disability Assessment for Dementia (DAD) Score Result | A questionaire filled in by the primary relative of the participant. DAD measures the impact of dementia symptoms on activities of daily living (ADL), including eating, dressing, personal hygiene. Total score ranges from 0 (worst) to 40 (best) | Posted | Mean | Standard Deviation | difference in DAD units on a scale | 1 year (enrollment in study and at 1-year follow-up) |
|
|
|
| Secondary | Change of Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Result | A questionaire filled in by the primary relative of the participant. NPI-Q measures the severity of neuropsychiatric symptoms of demented patients. The total score ranges between 0 (best) and (36 worst). | Posted | Mean | Standard Deviation | difference in NPI units on a scale | 1 year (enrollment in study and at 1-year follow-up) |
|
|
|
| Secondary | C2D6 Phenotype | Cyp2D6 is the gene which expresses the enzyme CYP2D6. Donepezil is metabolized by CYP2D6. | Posted | Count of Participants | Participants | For participants in the standard of care arm CYP2D6 status will be determined 1 year after enrollment. For participants in the intervention arm Cyp2D6 will be tested within 2 months if side effects are experienced, if not then after 6 months. |
|
|
|
| Secondary | Genetic Test for BcHE K Variant | BcHE butyryl cholinesterase (BChE), K variant. | Posted | Count of Participants | Participants | For participants in the standard of care arm BcHE K variant status will be tested 1 year after enrollment. For participants in the intervention arm BcHE K variant status will be determined at the 6 month follow-up. |
|
|
|
| Other Pre-specified | Genetic Test for APOe4 Allele Status. | The APOe4 allele is linked to an increased risk of developing Alzheimer's disease. | Posted | Count of Participants | Participants | For participants who complete the trial APOe4 allele status is assessed at the 1 year visit. |
|
|
|
| 2 |
| 65 |
| 6 |
| 65 |
| 42 |
| 65 |
| EG001 | Intervention Arm | Participants allocated to this arm follow are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention arm not experiencing side effects will have their treatment adjusted after 6 months based upon serum level of the drug in question. Donepezil: Adjustment of treatment with donepezil according to serum level. Memantine: Adjustment of treatment with memantine according to serum level. Measurement of serum level of anti-dementia drug: Participants allocated to the intervention arm are requested to inform the sponsor of any side effects up to 2 months after prescription of the anti-dementia drug. If so, they will have their treatment adjusted according to the serum level. Participants in the intervention group not experiencing side effects will have their treatment adjusted after 6 months based upon serum levels of the drug in question. Participants allocated to the standard of care arm follow the usual routines of the dementia clinic but are requested to have the serum level of the prescribed drug and CYP2D6-genotype measured after 12 month. | 2 | 67 | 7 | 67 | 46 | 67 |
| Psychosis | Psychiatric disorders | Systematic Assessment | Capgra syndrome |
|
| Psychosis | Psychiatric disorders | Systematic Assessment |
|
| Death | Surgical and medical procedures | Systematic Assessment | Fall causing hip fracture, resulting in death |
|
| Death | Vascular disorders | Systematic Assessment | Cardiac failure, anaemia |
|
| Donepezil overdose | General disorders | Systematic Assessment | Donepezil overdose (20 mg. daily for approx. 2 weeks) due to mistanke on part of the participant/relative. |
|
| COVID-19 | Infections and infestations | Systematic Assessment | COVID-19 respiratory infection |
|
| COVID-19 | Infections and infestations | Systematic Assessment | COVID-19 infection |
|
| Hospitalization due to headache | Nervous system disorders | Systematic Assessment | Tension-type headache |
|
| synkope | Vascular disorders | Systematic Assessment | Orthstatic Syncope |
|
| Stroke | Nervous system disorders | Systematic Assessment | Hospitalized due to stroke. Later death due to stroke complications. |
|
| Death due to lung cancer with metastases | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Diagnosed with lung cancer with cerebral metasteses after enrollment in study |
|
| Antebrachium facture | Surgical and medical procedures | Systematic Assessment | Antebrachium facture due to fall (bike accident) |
|
|
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| D001523 | Mental Disorders |
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D024801 | Tauopathies |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D000547 | Amantadine |
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
| Less regular |
|
| Irregular |
|
| Intermediate metabolizer |
|
| Poor metabolizer |
|
| mutant/mutant |
|
| APOE2/APOE4 |
|
| APOE3/APOE3 |
|
| APOE3/APOE4 |
|
| APOE4/APOE4 |
|