Trial Outcomes & Findings for PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations (NCT NCT02983058)

NCT ID: NCT02983058

Last Updated: 2020-06-02

Results Overview

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

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

12 participants

Primary outcome timeframe

90 minutes and the comparison will be binding in the specific regions listed (e.g., DLPFC) controlled by binding in the cerebellum/input function

Results posted on

2020-06-02

Participant Flow

Study subjects were exclusively recruited from the Amish and Mennonite community in Lancaster, Pennsylvania (PA). All subjects with psychotic spectrum disorder were receiving clinical care at the Clinic for Special Children in Strasburg, PA and identified an unaffected 1st or 2nd degree relative (unaffected subject).

All subjects (affected and unaffected) who met inclusion/exclusion criteria were included in the study.

Participant milestones

Participant milestones
Measure
Subjects With Psychotic Spectrum Disorders
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. PET/SPECT Scan: PET scan will be performed on a mCT scanner MRI Scan: Structural MRI will be obtained to permit co-registration of PET images
Unaffected 1st or 2nd Degree Relatives
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. PET/SPECT Scan: PET scan will be performed on a mCT scanner MRI Scan: Structural MRI will be obtained to permit co-registration of PET images
Overall Study
STARTED
7
5
Overall Study
COMPLETED
2
2
Overall Study
NOT COMPLETED
5
3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Subjects With Psychotic Spectrum Disorders
n=7 Participants
Subjects who met DSM-5 diagnostic criteria for psychotic disorder and had genetic confirmation of carrying CNTNAP2 mutation
Unaffected Relatives
n=5 Participants
Unaffected 1st or 2nd degree relatives of subjects who have psychotic spectrum disorder and carries the CNTNAP2 mutation. Unaffected relatives do not carry CNTNAP2 mutation
Total
n=12 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Age, Categorical
Between 18 and 65 years
7 Participants
n=99 Participants
5 Participants
n=107 Participants
12 Participants
n=206 Participants
Age, Categorical
>=65 years
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Sex: Female, Male
Female
2 Participants
n=99 Participants
3 Participants
n=107 Participants
5 Participants
n=206 Participants
Sex: Female, Male
Male
5 Participants
n=99 Participants
2 Participants
n=107 Participants
7 Participants
n=206 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
Asian
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
White
7 Participants
n=99 Participants
5 Participants
n=107 Participants
12 Participants
n=206 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Region of Enrollment
United States
7 participants
n=99 Participants
5 participants
n=107 Participants
12 participants
n=206 Participants

PRIMARY outcome

Timeframe: 90 minutes and the comparison will be binding in the specific regions listed (e.g., DLPFC) controlled by binding in the cerebellum/input function

Population: N was not reached and data was not analyzed

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

Outcome measures

Outcome measures
Measure
Subjects With Psychotic Spectrum Disorders
n=2 Participants
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. PET/SPECT Scan: PET scan will be performed on a mCT scanner MRI Scan: Structural MRI will be obtained to permit co-registration of PET images
Unaffected 1st or 2nd Degree Relatives
n=2 Participants
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. PET/SPECT Scan: PET scan will be performed on a mCT scanner MRI Scan: Structural MRI will be obtained to permit co-registration of PET images
Level of mGluR5 PET Binding in Dorsolateral Prefrontal Cortex (DLPFC) in CNTNAP2 Mutation Carriers vs. Comparison Subjects
13.58 mL/cm^3
Standard Deviation 1.27
11.12 mL/cm^3
Standard Deviation 0.24

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Subjects With Psychotic Spectrum Disorders
n=2 Participants
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. PET/SPECT Scan: PET scan will be performed on a mCT scanner MRI Scan: Structural MRI will be obtained to permit co-registration of PET images
Unaffected 1st or 2nd Degree Relatives
n=2 Participants
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. PET/SPECT Scan: PET scan will be performed on a mCT scanner MRI Scan: Structural MRI will be obtained to permit co-registration of PET images
Level of mGluR5 PET Binding in Hippocampus
10.61 mL/cm^3
Standard Deviation 1.60
11.29 mL/cm^3
Standard Deviation 0.53

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure
Subjects With Psychotic Spectrum Disorders
n=2 Participants
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. PET/SPECT Scan: PET scan will be performed on a mCT scanner MRI Scan: Structural MRI will be obtained to permit co-registration of PET images
Unaffected 1st or 2nd Degree Relatives
n=2 Participants
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. PET/SPECT Scan: PET scan will be performed on a mCT scanner MRI Scan: Structural MRI will be obtained to permit co-registration of PET images
Level of mGluR5 PET Binding in Primary Visual Cortex (Occipital Pole)
10.50 mL/cm^3
Standard Deviation 0.87
8.74 mL/cm^3
Standard Deviation 1.21

Adverse Events

Subjects With Psychotic Spectrum Disorders

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Unaffected 1st or 2nd Degree Relatives

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Marlene Carlson, MPH

New York State Psychiatric Institute

Phone: 646-774-8436

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place