Monitoring Anti-Dementia Drugs by Serum Levels

• Status: Recruiting
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The main objective of the MONANTI study is twofold:

Firstly, to determine the amount of the anti-dementia drugs donepezil and memantine in the blood (henceforth mentioned as 'serum level) 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 according to serum levels will benefit patients in terms of cognitive performance, quality of life, 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 serum-levels outside the recommended interval.

Thus, MONANTI will investigate if this is indeed the case in a broadly comprised population of patients suffering from dementia treated with donepezil or memantine. In addition, MONANTI will link serum levels to co-morbidity, level of compliance, medication interactions. It is hypothesized that the efficacy of anti-dementia medication can be significantly improved by adjustment of treatment according to serum levels. Also, it is hypothesized that the burden of side effects can be reduced in patients in whom too high serum levels are detected, if dosage 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 fit the enrollment criteria a patient must be newly diagnosed with either Alzheimer's disease, dementia with Lewy-bodies or Parkinson's disease with dementia and be described treatment with either donepezil or memantine. Also, the patient must not meet a list of (exclusion) criteria, which have been set up in order to avoid blur and biases of the results.

Patients can be selected as participators on account of the above, including an informed consent to participation. Next, the participators will randomized be assigned to one of two study arms. In the first of these, the control arm, the participators receive only standard treatment and follow-up at the outpatient clinic, except for measurement of serum level of the anti-dementia medication with which they are treated and a genetic test for a few key genes thought to be relevant for the study (two liver enzymes, two genes linked to Alzheimer's disease).

In the other arm, the intervention arm, the participators will be closely monitored for side effects after prescription of anti-dementia drugs. All these participators will be offered a measurement of serum level in case they experience possible side effects within 2 months of treatment initiation. If, not a measurement of the serum level will be done after 6 months. All patients in the intervention arm, will be offered adjustment of their treatment with the anti-dementia drug based upon serum level. To assess the possible effects of treatment adjustment seven clinical scoring tests will be used (MMSE, ACE, clock-drawing test, NPI-Q, DAD, GCI, GDS). Assessment includes symptom severity and level of compliance according to close relatives.

To measure the effect of donepezil on brain (cholinergic) function 30 participants will be recruited for electroencephalography (EEG). These participants will have an EEG done at enrollment and after 6 months.

In addition to the quantitative part study a qualitative part study with relatives of enrolled patients will be conducted.

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).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zealand University Hospital
• Collaborator: Epilepsihospitalet Filadelfia
• Treatments: Donepezil; Memantine

Criteria

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

• Alzheimer's disease

• dementia with Lewy Bodies

• Dementia in Parkinson's disease B. Participant must be prescribed either donepezil or memantine at enrollment. C. Participant must be able to give informed consent to participation in the study.

Exclusion Criteria:

• no accompanying relative at the enrollment and/or follow-up visits

• patients living alone who do not receive help to administer medication.

• lack of ability to cooperate, including severely reduced vision or impaired hearing and/or other severe disabilities.

• patients unable to give informed consent in a meaningful sense due to cognitive decline at enrollment.

• known psychiatric disease (schizophrenia, bipolar affective disorder etc.). However, patients suffering from depression are eligible if they have been in continuously medically treated for at least 3 months prior to enrollment.

• known neurologic disorder, which by it self could contribute to cognitive symptoms.

• other known medical condition (kidney-, liver-, metabolic disease etc.) which by itself could contribute to cognitive symptoms.

• treatment with anti-psychotic drugs within 3 months of possible enrollment. A minimal daily dosage of benzodiazepine is deemed permissable for enrollment.

• patients with a history of substantial previous abuse of alcohol or drugs. Also, any kind of substance abuse within last 3 months.

• any previous severe trauma to the head or neuroinfections which could contribute to cognitive symptoms.

• electro convulsive treatment within last 3 months.

• anesthesia within last 3 months