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

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ClinicalTrials.gov Identifier: NCT02061722
Recruitment Status : Completed
First Posted : February 13, 2014
Last Update Posted : June 1, 2016
Sponsor:
Information provided by (Responsible Party):
CHDI Foundation, Inc.

Tracking Information
First Submitted Date  ICMJE February 3, 2014
First Posted Date  ICMJE February 13, 2014
Last Update Posted Date June 1, 2016
Study Start Date  ICMJE January 2013
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2014)
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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02061722 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE [PETDE10] Imaging of PDE10A Enzyme Levels in Huntington's Disease Gene Expansion Carriers and Healthy Controls With PET.
Official Title  ICMJE [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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Huntington's Disease
Intervention  ICMJE 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%.

Study Arms  ICMJE 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%.

Intervention: Radiation: PET Imaging with [18F]MNI-659
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 11, 2016)
90
Original Estimated Enrollment  ICMJE
 (submitted: February 11, 2014)
60
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   Netherlands,   Norway,   Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02061722
Other Study ID Numbers  ICMJE CHDIKI1201/PET-HD-PDE10A
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CHDI Foundation, Inc.
Study Sponsor  ICMJE CHDI Foundation, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Bernhard Landwehrmeyer, MD, PhD Ulm University Hospital
Study Director: Cristina Sampaio, MD, PhD CHDI Foundation, Inc.
PRS Account CHDI Foundation, Inc.
Verification Date March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP