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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CHDI Foundation, Inc.
ClinicalTrials.gov Identifier:
NCT02061722
First received: February 3, 2014
Last updated: May 31, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Huntington's Disease
Radiation: PET Imaging with [18F]MNI-659
Phase 0

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by CHDI Foundation, Inc.:

Primary Outcome Measures:
  • 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. [ Time Frame: 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. ] [ Designated as safety issue: No ]

Enrollment: 90
Study Start Date: January 2013
Study Completion Date: May 2016
Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PET Imaging with [18F]MNI-659

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

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%.


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

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02061722

Locations
Denmark
The Memory Clinic, Rigshopitalet
Copenhagen, Denmark
Netherlands
Leiden University Medical Center, Department of Neurology
Leiden, Netherlands, K5Q112
Norway
University of Oslo, Nevrologisk poliklinikk
Oslo, Norway, 0372 Oslo
Sweden
Skane Universitetssjukhus Lund, Neurologiska kliniken
Lund, Sweden, SE-221 85
Karolinska Universitetssjukhus, Huddinge
Stockholm, Sweden, SE-141 86
Karolinska University Hospital
Stockholm, Sweden, SE-171 76
KTA Karolinska Trial Alliance
Stockholm, Sweden, SE-171 76
Neurologkliniken Akademiska sjukhuset, ing 85
Uppsala, Sweden, SE-751 85
Sponsors and Collaborators
CHDI Foundation, Inc.
Investigators
Principal Investigator: Bernhard Landwehrmeyer, MD, PhD Ulm University Hospital
Study Director: Cristina Sampaio, MD, PhD CHDI Foundation, Inc.
  More Information

Responsible Party: CHDI Foundation, Inc.
ClinicalTrials.gov Identifier: NCT02061722     History of Changes
Other Study ID Numbers: CHDIKI1201/PET-HD-PDE10A 
Study First Received: February 3, 2014
Last Updated: May 31, 2016
Health Authority: Sweden: Medical Products Agency

Additional relevant MeSH terms:
Huntington Disease
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
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Raclopride
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 25, 2016