Clinical trial NCT02061722: [PETDE10] Imaging of PDE10A Enzyme Levels in Huntington's Disease Gene Expansion Carriers and Healthy Controls With PET.
Official title: [PETDE10] Imaging of Phosphodiesterase 10 A (PDE10A) Enzyme Levels in the Living Human Brain of Huntington´s Disease Gene Expansion Carriers and Healthy Controls With Positron Emission Tomography
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Huntington's Disease
Lead sponsor: CHDI Foundation, Inc.
Sponsor class: OTHER
First posted: 2014-02-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The aim of this study is to measure the availability of the PDE10A enzyme in Huntington disease gene expansion carriers (HDGECs) using the recently developed radioligand \[18F\]MNI-659. The study will be cross-sectional, examining HDGECs at different stages of the disease (pre-manifest, stage 1 and stage 2), in comparison with Healthy Controls (HCs). The HDGECs included in this study will be recruited from the large database of the REGISTRY (NCT01590589) or ENROLL-HD (NCT01574053) studies.

Detailed description: The study will be organized in an "adaptive-like" mode. Initially a cohort of 5 HDGECs and 5 HCs will be studied. The data obtained in the first cohort will be analysed and depending on the variability of the data, there will be approximately 10 HDGECs and an equal number of HCs in the second cohort and the size of the third cohort may be altered to in total include approximately 45 HDGECs and an equal number of HCs.

Eligibility criteria: Inclusion Criteria:

* Capacity to give full informed consent in writing, and have read and signed the informed consent
* 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 co-morbidity of psychotic disorders, physical examination, vital signs and laboratory assessments
* 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 40 CAG repeats (HD stage 1: Total Functional Capacity (TFC) 11-13, HD stage 2: TFC 7-10); (B) Pre-manifest: Subjects that are carriers of the mutant Huntingtin gene with ≥40 CAG repeats, a disease burden score ≥ 275 (calculated by the equation ((CAGn-35.5) X age)), and a Total Motor Score (TMS) ≤ 5.

* Able and willing to travel to Stockholm
* Willing to comply with use of adequate contraceptive measures:

Exclusion Criteria:

* Any disease, condition or concomitant medications 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 the interpretation
* Regular use of any medication prohibited by this protocol with the exception for Viagra, Levitra and Cialis, which may be temporarily discontinued prior to the PET measurements
* HDGECs: History of other neurological condition (including brain surgery, intracranial haematoma, stroke/cerebrovascular disorders, epilepsy), co-morbidity of psychotic disorders
* HCs: Anamnesis/medical history of neurological conditions (Alzheimer´s disease, dementia, Parkinson´s disease, brain surgery, intracranial haematoma, stroke/cerebrovascular disorders, epilepsy) or psychiatric conditions schizophrenia, depression, bipolar disorder, attention-deficit hyperactivity disorder)
* HCs: Family history of HD
* History of or current alcohol or drug abuse or dependence
* History of anaphylactoid or anaphylactic reactions to any allergen including drugs and contrast media
* Haematological or biochemical parameters that are outside the normal range and are considered clinically significant by the Investigator
* Clinical relevant findings in the 12-lead ECG as determined by the evaluating physician
* Donation of blood (450 mL) within three months prior to Visit 3
* 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
* Participating in a clinical trial within the past 3 months
* HCs: previous participation in another PET study
* Positive viral test result for Hepatitis B or C or HIV 1 or 2
* Female subjects: breast-feeding or positive pregnancy test at screening or at Visit 3
* Contraindication for arterial cannulation (by assessment of Allen's test)

Primary outcomes:
measure: The primary outcome measure will be the distribution volume (VT) in the striatum (caudate and putamen), globus pallidus, and ventral striatum estimated using kinetic and graphical analysis. Thalamus, cortex and cerebellum will also be examined.
timeFrame: Visit 3: For HD subjects, this will occur within 90 days from the Screening Visit. For Healthy Controls, this will occur within 28 days of Screening visit.
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: The Memory Clinic, Rigshopitalet
city: Leiden
country: Netherlands
facility: Leiden University Medical Center, Department of Neurology
city: Oslo
country: Norway
facility: University of Oslo, Nevrologisk poliklinikk
city: Lund
country: Sweden
facility: Skane Universitetssjukhus Lund, Neurologiska kliniken
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhus, Huddinge
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: KTA Karolinska Trial Alliance
city: Uppsala
country: Sweden
facility: Neurologkliniken Akademiska sjukhuset, ing 85
Study officials:
affiliation: Ulm University Hospital
name: Bernhard Landwehrmeyer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHDI Foundation, Inc.
name: Cristina Sampaio, MD, PhD
role: STUDY_DIRECTOR
References: