neurodegenerative movement disorder
Conditions
Interventions
None listed
Sponsors
CHDI foundation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Age 18 to 70 years, inclusive;- (HCs): Healthy according to medical history, physical examination, ECG, vital signs, laboratory assessment and MRI, with a body mass index between 19 and 27 (both inclusive);- HDGECs: Otherwise healthy according to medical history, no comorbidity of psychotic disorders, physical examination, vital signs and laboratory assessments, and with a body mass index (BMI) between 19 and 27 (both inclusive) - (HDGECs): (A) HD Stage 1 or HD Stage 2: Patients with a clinical diagnosis of HD, defined by the presence of noticeable motor disorder and *36 CAG repeats (HD stage 1: TFC 11-13, HD stage 2: TFC 7-10); (B) Pre-manifest: Subjects that are carriers of the mutant Huntington gene with *40 CAG repeats, a Total Motor Score *5 and disease burden score of either * 250 (early pre-manifest) or a disease burden score * 275 (late pre-manifest); disease burden score is calculated with the equationa ((CAGn-35.5) X age))
Exclusion criteria
Exclusion criteria: - HDGECs and HCs: Any disease, condition, or concomitant medication that significantly compromises the function of the body systems and that in the opinion of the Investigator might interfere with the conduct of the study or its interpretation.;- History of anaphylactoid or anaphylactic reactions to any allergen including drugs and contrast media.;- Contraindication to MRI, such as known claustrophobia, presence of metal devises or implants (e.g. pacemaker, vascular- or heart- valves, stents, clips), metal deposited in the body (e.g. bullets or shells), or metal grains in the eyes.;- HDGECs: History of other neurological condition (including brain surgery, intracranial haematoma, stroke/cerebrovascular disorders, epilepsy), co-morbidity of psychotic disorders.;- HCs: Family history of HD.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective is to measure the availability of the PDE10A enzyme in Huntington*s Disease (HD)gene expansion carriers (HDGECs) by estimating and comparing the distribution volume (VT) of the radioligand [18F]MNI-659 in the striatum (caudate and putamen), globus pallidus, ventral striatum including nucleus accumbens, thalamus, cortex and cerebellum in HDGECs and age (± 5 years)- and gender-matched healthy controls (HCs). | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives are (as have been described above): 1) To compare the non-displaceable distribution volume (VND) of [18F]MNI-659 in the cerebellum between HDGECs and HCs. If no differences in the VND will be found, the cerebellum will be considered as reference region and the binding potential (BPND) will be estimated as: (VT-VND)/VND and with the simplified reference tissue model SRTM and with the non-invasive Logan graphical analysis. 2) To compare the kinetics, metabolism and the protein binding of the [18F]MNI-659 in HDGECS and HCs. 3) To compare the availability of the PDE10A enzyme in sub-divisions of the striatum (caudate, putamen and ventral striatum including nucleus accumbens) with the D2 receptor availability in the same regions in HDGECs and HCs. 4) To explore the correlation between the availability of the PDE10A enzyme (VT or BPND) and the number of CAG repeats in HDGECs. 5) To explore the correlation between the availability of the PDE10A enzyme (VT or BPND) in HDGECs and disease duration (the classical definition of time when motor clinical manifestation first became noticeable will be used), clinical ratings (stage and Unified Huntington*s Disease Rating Scale [UHDRS]), functional assessments (Total Motor Score [TMS] and Total Functional Capacity [TFC]) and psychiatric and cognitive assessments (Cognitive Battery Assessment [CBA]). | — |
Countries
Netherlands
Outcome results
None listed