PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations

May 19, 2020 updated by: Jeffrey A. Lieberman, MD
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 59 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
OTHER: PET/SPECT and MRI scans
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.
Radiation: PET/SPECT Scan
PET scan will be performed on a mCT scanner
Other Names:
  • PET
Device: MRI Scan
Structural MRI will be obtained to permit co-registration of PET images
Other Names:
  • MRI

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Level of mGluR5 PET Binding in Dorsolateral Prefrontal Cortex (DLPFC) in CNTNAP2 Mutation Carriers vs. Comparison Subjects
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
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
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 Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Level of mGluR5 PET Binding in Hippocampus
Time Frame: 90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function
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.
90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function
Level of mGluR5 PET Binding in Primary Visual Cortex (Occipital Pole)
Time Frame: 90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function
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).
90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jeffrey A. Lieberman, MD

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sander Markx, MD, New York State Psychiatric Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 25, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 6, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 2, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • #7107

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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