HD-med: A longitudinal, observational study to assess medication use, medication efficacy and the role of pharmacogenetics in Huntington*s Disease.

Rationale: Huntington*s disease (HD) is a hereditary, neurodegenerative
disorder characterized by motor, cognitive and psychiatric symptoms. Currently,
HD can only be managed symptomatically, including a large variety in prescribed
drugs. Many HD patients experience negative medication effects (e.g.
side-effects or non-response). Pharmacogenetic (PGx) studies show how
individual genetic differences affect medication efficacy and toxicity, and
holds the potential to explain and resolve these negative medication effects.
This study aims to characterize which part of negative medication effects can
be resolved by implementing PGx testing. The ultimate goal is to better guide
the long-term pharmacological management of HD in a more personalized manner by
predicting the individual patient*s risk of negative medication effects.

Primary objective: To classify the effect of the pharmacogenetic profile of
CYP2C19 and CYP2D6 in HD gene carriers, compared to more classic medication
prescribing parameters (such as age and comorbidities) on negative medication
effects of HD-related medication. Negative medication effects are classified as
non-response or side effects of the prescribed drug, which lead to definite
prescription changes in that drug. Definite prescription changes are classified
as; discontinuation of the drug, switching to another type of drug or adding
another drug to treat the same symptom.

Secondary objectives:
- To assess and categorize current medication use in HD gene carriers.
- To determine the eligibility of a one-year medication diary compared to
pharmacy medication history surveys in HD patients.
- To classify the effect of the pharmacogenetic profile of CYP2C19 and CYP2D6
in HD gene carriers who are on HD-related medication and who either use a
relatively low or a relatively high drug dose with regard to the symptom the
drug is prescribed for.

Explorative objective:
- To explore potential new genetic polymorphisms with pharmacogenetic action in
HD gene carrier subgroups with an extra-ordinary side effect profile or lack of
medication response.

Longitudinal, observational, mulit-center study.

During baseline visit at the outpatient clinic, subjects are asked to fill in a
medication questionnaire and have a neurological and neuropsychologic
examination. Furthermore, a single blood sample (4 ml) for pharmacogenetic
analysis will be drawn. During follow-up, subjects record their medication
changes in a diary. Five telephone calls are performed to map any changes in
medication use or general health. At baseline and after one year, a medication
verification scheme is requested at subjects* local pharmacy. A negligible risk
is attached to blood drawing, furthermore no risks are attached to this study
and patient burden is considered to be low.