[PETDE10] Imaging of PDE10A Enzyme Levels in Huntington's Disease Gene Expansion Carriers and Healthy Controls With PET.

NCT02061722 | Completed Early Phase 1 DMC

• 1 other identifier: CHDIKI1201/PET-HD-PDE10A
• Study Type: interventional
• Target: 90
• Locations: 4 countries
• Sites: 8

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.

Conditions

Huntington's Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Study Arms (1)

PET Imaging with [18F]MNI-659

EXPERIMENTAL

All subjects (both HDGECs and HCs) will receive single intravenous doses of the radioligands \[11C\]raclopride (non-investigational medicinal product \[NIMP\]) and \[18F\]MNI-659 (investigational medicinal product \[IMP\]). The radioligands \[11C\]raclopride and \[18F\]MNI-659 will be administered at doses less than 10 micrograms, i.e. within the micro dosing concept, and no pharmacological effects are expected. The injected radioactivity of \[11C\]raclopride will be 300 MBq/70 kg of body weight ± 10%. The injected radioactivity of \[18F\]MNI-659 will be 185 MBq/70 kg of body weight ± 10%.

Radiation: PET Imaging with [18F]MNI-659

Interventions

PET Imaging with [18F]MNI-659 RADIATION

The radioligands \[11C\]raclopride and \[18F\]MNI-659 will be administered at doses less than 10 micrograms, i.e. within the micro dosing concept, and no pharmacological effects are expected. The injected radioactivity of \[11C\]raclopride will be 300 MBq/70 kg of body weight ± 10%. The injected radioactivity of \[18F\]MNI-659 will be 185 MBq/70 kg of body weight ± 10%.

PET Imaging with [18F]MNI-659

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• CHDI Foundation, Inc.: lead

Study Sites (8)

The Memory Clinic, Rigshopitalet

Copenhagen, Denmark

Location

Leiden University Medical Center, Department of Neurology

Leiden, K5Q112, Netherlands

Location

University of Oslo, Nevrologisk poliklinikk

Oslo, 0372 Oslo, Norway

Location

Skane Universitetssjukhus Lund, Neurologiska kliniken

Lund, SE-221 85, Sweden

Location

Karolinska Universitetssjukhus, Huddinge

Stockholm, SE-141 86, Sweden

Location

Karolinska University Hospital

Stockholm, SE-171 76, Sweden

Location

KTA Karolinska Trial Alliance

Stockholm, SE-171 76, Sweden

Location

Neurologkliniken Akademiska sjukhuset, ing 85

Uppsala, SE-751 85, Sweden

Location

MeSH Terms

Conditions

Huntington Disease

Interventions

Magnetic Resonance Spectroscopy; 2-(2-(3-(4-(2-fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Bernhard Landwehrmeyer, MD, PhD

  Ulm University Hospital

  PRINCIPAL INVESTIGATOR

• Cristina Sampaio, MD, PhD

  CHDI Foundation, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2014
• First Posted: February 13, 2014
• Study Start: January 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: June 1, 2016

Record last verified: 2016-03

Locations

NO (1); SE (5); NL (1); DK (1)