Follow-up Measurement of Brain PDE10A Enzyme Levels in Huntington´s Disease Gene Expansion Carriers (LONGPDE10)

Follow-up Measurement of Brain Phosphodiesterase 10 A (PDE10A) Enzyme Levels in Huntington´s Disease Gene Expansion Carriers, 18 to 28 Months After Initial Positron Emission Tomography (PET) Measurement in CHDIKI1201/PET-HD-PDE10A (NCT02061722)

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.

Study Overview

• Status: Completed
• Conditions: Huntington's Disease
• Intervention / Treatment: Radiation: Radioligand [18F]MNI-659

Detailed Description

The HDGECs will perform 2 study visits: Visit 1 (screening) and Visit 2 (PET analysis utilizing the radioligand [18F]MNI-659). There will also be 2 telephone follow ups; one after Visit 1 (telephone follow-up after screening) and one after Visit 2, (telephone follow-up after PET). Study visits and telephone follow-ups will take place during a maximum of 97 days.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • The Memory Clinic, Rigshopitalet
• Netherlands
  • Leiden, Netherlands, K5Q112
    • Leiden University Medical Center, Department of Neurology
• Norway
  • Oslo, Norway, 0372 Oslo
    • University of Oslo, Nevrologisk poliklinikk
• Sweden
  • Lund, Sweden, SE-221 85
    • Skane Universitetssjukhus Lund, Neurologiska kliniken
  • Stockholm, Sweden, SE-171 76
    • Karolinska University Hospital
  • Stockholm, Sweden, SE-141 86
    • Karolinska Universitetssjukhus, Huddinge
  • Uppsala, Sweden
    • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 73 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

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 (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Radioligand [18F]MNI-659; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: CHDI Foundation, Inc.
• Investigators: Principal Investigator: Andrea Varrone, MD, PhD, Karolinska University Hospital; Study Director: Cristina Sampaio, MD, PhD, CHDI Foundation, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 6, 2015
• Primary Completion (ACTUAL): October 5, 2017
• Study Completion (ACTUAL): October 5, 2017

Study Registration Dates

• First Submitted: March 11, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (ESTIMATE): November 6, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 10, 2019
• Last Update Submitted That Met QC Criteria: October 8, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: CHDIKI1401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO