Follow-up Measurement of Brain PDE10A Enzyme Levels in Huntington´s Disease Gene Expansion Carriers (LONGPDE10)
Primary Purpose
Huntington's Disease
Status
Completed
Phase
Early Phase 1
Locations
International
Study Type
Interventional
Intervention
Radioligand [18F]MNI-659
Sponsored by
About this trial
This is an interventional diagnostic trial for Huntington's Disease
Eligibility Criteria
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
Sites / Locations
- The Memory Clinic, Rigshopitalet
- Leiden University Medical Center, Department of Neurology
- University of Oslo, Nevrologisk poliklinikk
- Skane Universitetssjukhus Lund, Neurologiska kliniken
- Karolinska Universitetssjukhus, Huddinge
- Karolinska University Hospital
- Uppsala University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Radioligand [18F]MNI-659
Arm Description
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%.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02956148
Brief Title
Follow-up Measurement of Brain PDE10A Enzyme Levels in Huntington´s Disease Gene Expansion Carriers
Acronym
LONGPDE10
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
September 6, 2015 (Actual)
Primary Completion Date
October 5, 2017 (Actual)
Study Completion Date
October 5, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CHDI Foundation, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington's Disease
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Radioligand [18F]MNI-659
Arm Type
Experimental
Arm Description
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%.
Intervention Type
Radiation
Intervention Name(s)
Radioligand [18F]MNI-659
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
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
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
73 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Varrone, MD, PhD
Organizational Affiliation
Karolinska University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Cristina Sampaio, MD, PhD
Organizational Affiliation
CHDI Foundation, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
The Memory Clinic, Rigshopitalet
City
Copenhagen
Country
Denmark
Facility Name
Leiden University Medical Center, Department of Neurology
City
Leiden
ZIP/Postal Code
K5Q112
Country
Netherlands
Facility Name
University of Oslo, Nevrologisk poliklinikk
City
Oslo
ZIP/Postal Code
0372 Oslo
Country
Norway
Facility Name
Skane Universitetssjukhus Lund, Neurologiska kliniken
City
Lund
ZIP/Postal Code
SE-221 85
Country
Sweden
Facility Name
Karolinska Universitetssjukhus, Huddinge
City
Stockholm
ZIP/Postal Code
SE-141 86
Country
Sweden
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
SE-171 76
Country
Sweden
Facility Name
Uppsala University Hospital
City
Uppsala
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Follow-up Measurement of Brain PDE10A Enzyme Levels in Huntington´s Disease Gene Expansion Carriers
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