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).