PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations
Primary Purpose
Schizophrenia
Status
Terminated
Phase
Phase 1
Locations
United States
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
- Aged 18-59 years
- Genetic confirmation that patient carries CNTNAP2 mutation
- All patients will be 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 Columbia University Medical Center in New York City and back to Lancaster, PA
- In the judgment of the participant's treating physician as well as the evaluating consenter, the patient is stable enough to travel and participate in the study
Control subjects:
- Aged 18-59 years
- 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, including cannabinoids, amphetamine, benzodiazepines, barbiturates, cocaine, methadone, opiates, and phencyclidine
- 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. However, in case of previous exposure to radioactivity due to research studies, subjects will be eligible if all conditions listed below are fulfilled:
- research studies in question have been performed in the context of a protocol from the Division of Translational Imaging (Anissa Abi-Dargham, M.D., Director) or as part of a research study within another division at Columbia University/NYSPI and the injected dose and dosimetry of the radiotracer are known
- Except for research studies, the patient has had no lifetime exposure to radiation in the workplace or in nuclear medicine procedures
- Adding the previous exposure to the exposure due to this study will result in a yearly cumulative exposure lower than the limit defined by the FDA for research subjects
- Blood donation within 8 weeks of study
- Presence of clinically significant brain abnormalities
- For female patients 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 PET scan based on a serum pregnancy test. Women who are breast-feeding are also excluded.
- Metal implants, pacemaker, 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, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologist: "Guide to MR procedures and metallic objects", F.G. Shellock, Lippincott Williams and Wilkins NY 2001.
- 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
- New York State Psychiatric Insitute
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 minute 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 CNTNAP mutation carriers vs comparison subjects
Evaluate the utility of mGluR5 binding as measured by PET as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation.
Secondary Outcome Measures
Level of mGluR5 PET binding in hippocampus and primary visual cortex (occipial pole)
Evaluate PET mGluR5 binding in other regions of potential relevance, including hippocampus and primary visual cortex in order to determine ideal regions of interest for future intervention studies
Full Information
NCT ID
NCT02572206
First Posted
September 28, 2015
Last Updated
September 26, 2016
Sponsor
New York State Psychiatric Institute
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT02572206
Brief Title
PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations
Official Title
Demonstration of mGluR5 Overexpression in Amish and Mennonite CNTNAP2 Mutation Carriers
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
NIMH terminated study
Study Start Date
September 2015 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New York State Psychiatric Institute
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Data Monitoring Committee
Yes
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 a 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 (NYPSI) and the Research Foundation for Mental Hygiene Inc (RFMH) and will take place at Columbia University Medcial 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 Old-Order Amish control patients drawn from the same families but not harboring CNTNAP2 mutations (n=20). The primary measure will consist of mGluR5 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
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (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 minute 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 CNTNAP mutation carriers vs comparison subjects
Description
Evaluate the utility of mGluR5 binding as measured by PET as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation.
Time Frame
90 minutes and the comparison will be binding in the specific regions listed (e.g., dorsolateral prefrontal cortex) controlled by binding in the cerebellum/input function.
Secondary Outcome Measure Information:
Title
Level of mGluR5 PET binding in hippocampus and primary visual cortex (occipial pole)
Description
Evaluate PET mGluR5 binding in other regions of potential relevance, including hippocampus and primary visual cortex in order to determine ideal regions of interest for future intervention studies
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
Aged 18-59 years
Genetic confirmation that patient carries CNTNAP2 mutation
All patients will be 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 Columbia University Medical Center in New York City and back to Lancaster, PA
In the judgment of the participant's treating physician as well as the evaluating consenter, the patient is stable enough to travel and participate in the study
Control subjects:
Aged 18-59 years
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, including cannabinoids, amphetamine, benzodiazepines, barbiturates, cocaine, methadone, opiates, and phencyclidine
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. However, in case of previous exposure to radioactivity due to research studies, subjects will be eligible if all conditions listed below are fulfilled:
research studies in question have been performed in the context of a protocol from the Division of Translational Imaging (Anissa Abi-Dargham, M.D., Director) or as part of a research study within another division at Columbia University/NYSPI and the injected dose and dosimetry of the radiotracer are known
Except for research studies, the patient has had no lifetime exposure to radiation in the workplace or in nuclear medicine procedures
Adding the previous exposure to the exposure due to this study will result in a yearly cumulative exposure lower than the limit defined by the FDA for research subjects
Blood donation within 8 weeks of study
Presence of clinically significant brain abnormalities
For female patients 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 PET scan based on a serum pregnancy test. Women who are breast-feeding are also excluded.
Metal implants, pacemaker, 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, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologist: "Guide to MR procedures and metallic objects", F.G. Shellock, Lippincott Williams and Wilkins NY 2001.
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
Jeffrey A Lieberman, MD
Organizational Affiliation
New York State Psychiatric Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York State Psychiatric Insitute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
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