Back to resultsPET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations
Primary Purpose
Schizophrenia
Status
Terminated
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
PET/SPECT Scan
MRI Scan
Sponsored by
About this trial
This is an interventional basic science trial for Schizophrenia
Eligibility Criteria
Inclusion Criteria:
Patients:
- Meets DSM-5 diagnostic criteria for psychotic disorder, including schizophrenia, schizoaffective disorder or psychotic disorder not elsewhere classified
- Genetic confirmation that patient carries CNTNAP2 mutation
- Of Amish and/or Mennonite descent
- Has a relative willing to be part of the study and this relative will travel with the participant to CUMC in NYC and back to Lancaster, PA
- Stable enough to travel and participate in the study
Control subjects:
- Genetic confirmation that subject does not carry CNTNAP2 mutation
- First-degree or second-degree relative of subject of Amish/Mennonite descent with CNTNAP2 mutation
Exclusion Criteria (for patients and controls):
- Positive urine toxicology for drugs of abuse
- Positive history of severe neurological illness or history of brain trauma
- Positive history of severe medical illness that would increase risk due to PET scan procedure, or interfere with interpretation of research findings
- Low hemoglobin (Hb < 11 g/dL in males, Hb < 10 g/dL in females)
- Lifetime exposure to radiation in the workplace, or lifetime history of participation in nuclear medicine procedures, including research protocols.
- Blood donation within 8 weeks of study
- Presence of clinically significant brain abnormalities
- Female subjects of child-bearing age who are not surgically sterilized and between menarche and 1 year postmenopausal must test negative for pregnancy at the time of enrollment and prior to the PET scan based on a serum pregnancy test. Women who are breast-feeding are also excluded.
- Metal implants, pacemakers, other metal (e.g., shrapnel or surgical prostheses) or paramagnetic objects contained within the body which may present a risk to the subject or interfere with the MR scan
- Medicinal patch, unless removed prior to the MR scan
- Patients: current treatment with clozapine and/or medications other than antipsychotics PRN anxiolytics
- Use of the medications that would interfere with mGluR5 binding, including lamotrigine, gabapentin, topiramate, phenobarbital, pregabalin, zonisamide, N-acetylcysteine, D-cycloserine
- Control subjects: lifetime history of antipsychotic or antidepressant use
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
PET/SPECT and MRI scans
Arm Description
PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.
Outcomes
Primary Outcome Measures
Level of mGluR5 PET Binding in Dorsolateral Prefrontal Cortex (DLPFC) in CNTNAP2 Mutation Carriers vs. Comparison Subjects
Outcome measure is total distribution volume (VT) where distribution volume of the non displaceable compartment (VND) plus binding potential (BPP) with respect to the arterial plasma concentration of tracer. VT=VND + BPP
Secondary Outcome Measures
Level of mGluR5 PET Binding in Hippocampus
Evaluate PET mGluR5 binding in other regions of potential relevance, including hippocampus in order to determine ideal regions of interest for future intervention studies by using VT=VND + BPP. VND is assumed to be equal across brain regions and therefore VT will vary across brain regions with mGluR5 concentration.
Level of mGluR5 PET Binding in Primary Visual Cortex (Occipital Pole)
Evaluate PET mGluR5 binding in other regions of potential relevance, including primary visual cortex in order to determine ideal regions of interest for future intervention studies as measured by total distribution volume (VT).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02983058
Brief Title
PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations
Official Title
PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Terminated
Why Stopped
To obtain funding for a larger study
Study Start Date
November 2016 (undefined)
Primary Completion Date
July 2017 (Actual)
Study Completion Date
July 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jeffrey A. Lieberman, MD
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary goal of the present study is to evaluate the utility of mGluR5 binding as measured by PET as biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation.
Detailed Description
The investigators will focus on mGluR5 PET binding as a surrogate measure for level of activity of the mTOR kinase pathway. This study is being conducted by the New York State Psychiatric Institute (NYSPI) and will take place at Columbia University Medical Center (CUMC) in New York City and at a research office in Strasburg, PA. Subjects (n=20) with the CNTNAP2 mutation with schizophrenia or a related condition will be recruited from the Amish and Mennonite communities and brought to CUMC for detailed investigation. Affected individuals will be compared to Amish and Mennonite control subjects drawn from the same families but not harboring CNTNAP2 mutations (n=20). The primary measure will consist of mGluR PET binding in DLPFC. In addition, secondary analyses will assess binding in other brain regions such as hippocampus and visual cortex. Exploratory measures, as well as relationships between PET mGluR5 binding and clinical symptomatology, will be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PET/SPECT and MRI scans
Arm Type
Other
Arm Description
PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.
Intervention Type
Radiation
Intervention Name(s)
PET/SPECT Scan
Other Intervention Name(s)
PET
Intervention Description
PET scan will be performed on a mCT scanner
Intervention Type
Device
Intervention Name(s)
MRI Scan
Other Intervention Name(s)
MRI
Intervention Description
Structural MRI will be obtained to permit co-registration of PET images
Primary Outcome Measure Information:
Title
Level of mGluR5 PET Binding in Dorsolateral Prefrontal Cortex (DLPFC) in CNTNAP2 Mutation Carriers vs. Comparison Subjects
Description
Outcome measure is total distribution volume (VT) where distribution volume of the non displaceable compartment (VND) plus binding potential (BPP) with respect to the arterial plasma concentration of tracer. VT=VND + BPP
Time Frame
90 minutes and the comparison will be binding in the specific regions listed (e.g., DLPFC) controlled by binding in the cerebellum/input function
Secondary Outcome Measure Information:
Title
Level of mGluR5 PET Binding in Hippocampus
Description
Evaluate PET mGluR5 binding in other regions of potential relevance, including hippocampus in order to determine ideal regions of interest for future intervention studies by using VT=VND + BPP. VND is assumed to be equal across brain regions and therefore VT will vary across brain regions with mGluR5 concentration.
Time Frame
90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function
Title
Level of mGluR5 PET Binding in Primary Visual Cortex (Occipital Pole)
Description
Evaluate PET mGluR5 binding in other regions of potential relevance, including primary visual cortex in order to determine ideal regions of interest for future intervention studies as measured by total distribution volume (VT).
Time Frame
90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Patients:
Meets DSM-5 diagnostic criteria for psychotic disorder, including schizophrenia, schizoaffective disorder or psychotic disorder not elsewhere classified
Genetic confirmation that patient carries CNTNAP2 mutation
Of Amish and/or Mennonite descent
Has a relative willing to be part of the study and this relative will travel with the participant to CUMC in NYC and back to Lancaster, PA
Stable enough to travel and participate in the study
Control subjects:
Genetic confirmation that subject does not carry CNTNAP2 mutation
First-degree or second-degree relative of subject of Amish/Mennonite descent with CNTNAP2 mutation
Exclusion Criteria (for patients and controls):
Positive urine toxicology for drugs of abuse
Positive history of severe neurological illness or history of brain trauma
Positive history of severe medical illness that would increase risk due to PET scan procedure, or interfere with interpretation of research findings
Low hemoglobin (Hb < 11 g/dL in males, Hb < 10 g/dL in females)
Lifetime exposure to radiation in the workplace, or lifetime history of participation in nuclear medicine procedures, including research protocols.
Blood donation within 8 weeks of study
Presence of clinically significant brain abnormalities
Female subjects of child-bearing age who are not surgically sterilized and between menarche and 1 year postmenopausal must test negative for pregnancy at the time of enrollment and prior to the PET scan based on a serum pregnancy test. Women who are breast-feeding are also excluded.
Metal implants, pacemakers, other metal (e.g., shrapnel or surgical prostheses) or paramagnetic objects contained within the body which may present a risk to the subject or interfere with the MR scan
Medicinal patch, unless removed prior to the MR scan
Patients: current treatment with clozapine and/or medications other than antipsychotics PRN anxiolytics
Use of the medications that would interfere with mGluR5 binding, including lamotrigine, gabapentin, topiramate, phenobarbital, pregabalin, zonisamide, N-acetylcysteine, D-cycloserine
Control subjects: lifetime history of antipsychotic or antidepressant use
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sander Markx, MD
Organizational Affiliation
New York State Psychiatric Institute
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations
We'll reach out to this number within 24 hrs