Follow-up Measurement of Brain PDE10A Enzyme Levels in Huntington´s Disease Gene Expansion Carriers

NCT02956148 | Completed Early Phase 1

• 1 other identifier: CHDIKI1401
• Study Type: interventional
• Target: 45
• Locations: 4 countries
• Sites: 7

Brief Summary

The aim of this study is to measure longitudinally the availability of the PDE10A enzyme in HDGECs using the radioligand \[18F\]MNI-659. The study will be a follow-up, examining HDGECs from the CHDIKI1201/PET-HD-PDE10A (NCT02061722) study from 18 to 28 months after the initial PET measurement.

Conditions

Huntington's Disease

Outcome Measures

Primary Outcomes (1)

• The longitudinal changes of PDE10A enzyme availability in the caudate, putamen, and globus pallidus of Huntington's Disease Gene Expansion Carriers by comparison of the follow-up and initial PET measurements.

  The HDGECs will perform 2 study visits; Visits 1 (screening) and Visit 2 (PET) and 2 telephone follow ups, one after Visit 1 (telephone follow-up after screening) and one after Visit 2, (telephone follow-up after PET) 18 to 28 months after the initial PET measurement conducted in the CHDIKI1201/PET-HD-PDE10A study. An individual subject's participation in this study will last for a maximum of 97 days

  The follow up PET measurement can be performed from 18 to 28 months after the initial PET measurement that was performed in the CHDIKI/PET-HD-PDE10A Study

Study Arms (1)

Radioligand [18F]MNI-659

EXPERIMENTAL

All subjects will receive a single intravenous dose of the radioligand \[18F\]MNI-659 (investigational medicinal product \[IMP\]) and undergo PET imaging. The radioligand \[18F\]MNI-659 will be administered at a dose of less than 5 micrograms, i.e. within the micro dosing concept, and no pharmacological effects are expected. The injected radioactivity of \[18F\]MNI-659 will be 185 MBq/70 kg of body weight ± 10%.

Radiation: Radioligand [18F]MNI-659

Interventions

Radioligand [18F]MNI-659 RADIATION

The effective radiation dose for the injection of \[18F\]MNI-659 is approximately 5.6 mSv (approximately 2 years of background radiation in Sweden) for an average person weighing 70 kg.

Radioligand [18F]MNI-659

Eligibility Criteria

• Age: 18 Years - 73 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have participated in and completed study CHDIKI1201/PET-HD-PDE10A and are capable of providing informed consent or have a legal representative authorized to give consent on their behalf.
• Otherwise healthy according to medical history, no co-morbidity of psychotic disorders, physical examination, vital signs and laboratory assessments
• Willing to travel to Stockholm (with a companion if requested) for PET examinations
• Suitable physically and psychologically to travel to Stockholm and undergo PET examinations, as judged by the recruiting Investigator with attention given to symptoms of chorea and anxiety
• Willing to comply with the 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 (selective or non-selective PDE inhibitors), with the exception for erectile dysfunction medication, which may be temporarily discontinued prior to the PET measurement
• History of anaphylactoid or anaphylactic reactions to any allergen including drugs and contrast media
• History of other neurological condition (including brain surgery, intracranial hematoma, stroke/cerebrovascular disorders, epilepsy), co-morbidity of psychiatric disorders
• Clinically relevant findings in hematological, biochemical testing or 12-lead ECG as determined by the evaluating physician
• Female subjects who are breast-feeding or have a positive pregnancy test at screening or at Visit 2

Sponsors & Collaborators

• CHDI Foundation, Inc.: lead

Study Sites (7)

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

Uppsala University Hospital

Uppsala, Sweden

Location

MeSH Terms

Conditions

Huntington Disease

Interventions

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

Study Officials

• Andrea Varrone, MD, PhD

  Karolinska 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: March 11, 2016
• First Posted: November 7, 2016
• Study Start: September 6, 2015
• Primary Completion: October 5, 2017
• Study Completion: October 5, 2017
• Last Updated: October 10, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); DK (1); NO (1); SE (4)