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Trial Outcomes & Findings for I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers (NCT NCT02323217)

NCT ID: NCT02323217

Last Updated: 2021-11-15

Results Overview

The determination of the regional density and distribution of the I2BS in human brain of healthy volunteers. The output parameter used to determine this will be derived from the most appropriate PET pharmacokinetic model for this ligand in human e.g. Total Volume of Distribution (VT) or Binding Potential (BP). Regional time-activity data were generated from arterial plasma input functions corrected for metabolites using the most appropriate model to derive the outcome measure VT (regional distribution volume). All image processing and kinetic analyses were performed in MIAKAT. The Akaike model selection criteria were used to determine the most appropriate model to describe these data. The calculated criteria for the three main models are: one-tissue (1TCM) and two-tissue (2TCM) compartmental models, and multilinear analysis model (MA).

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

20 participants

Primary outcome timeframe

1 week

Results posted on

2021-11-15

Participant Flow

Participant milestones

Participant milestones
Measure
Healthy Volunteers
\[11C\]BU99008: Baseline Scan, Test-ReTest or Dosimetry Idazoxan: Idazoxan block of \[11C\]BU99008 Isocarboxazid: Isocarboxazid block of \[11C\]BU99008
Overall Study
STARTED
18
Overall Study
COMPLETED
18
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Healthy Volunteers
n=18 Participants
\[11C\]BU99008: Baseline Scan, Test-ReTest or Dosimetry Idazoxan: Idazoxan block of \[11C\]BU99008 Isocarboxazid: Isocarboxazid block of \[11C\]BU99008
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
18 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
Sex: Female, Male
Male
18 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 1 week

The determination of the regional density and distribution of the I2BS in human brain of healthy volunteers. The output parameter used to determine this will be derived from the most appropriate PET pharmacokinetic model for this ligand in human e.g. Total Volume of Distribution (VT) or Binding Potential (BP). Regional time-activity data were generated from arterial plasma input functions corrected for metabolites using the most appropriate model to derive the outcome measure VT (regional distribution volume). All image processing and kinetic analyses were performed in MIAKAT. The Akaike model selection criteria were used to determine the most appropriate model to describe these data. The calculated criteria for the three main models are: one-tissue (1TCM) and two-tissue (2TCM) compartmental models, and multilinear analysis model (MA).

Outcome measures

Outcome measures
Measure
Healthy Volunteers
n=18 Participants
\[11C\]BU99008: Baseline Scan, Test-ReTest or Dosimetry Idazoxan: Idazoxan block of \[11C\]BU99008 Isocarboxazid: Isocarboxazid block of \[11C\]BU99008
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Whole Brain
44.5 mL/cm^3
Standard Deviation 6.1
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Hippocampus
68.4 mL/cm^3
Standard Deviation 11.4
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Thalamus
75.3 mL/cm^3
Standard Deviation 11.0
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Cerebellum
39.3 mL/cm^3
Standard Deviation 6.2
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Brain stem
62.7 mL/cm^3
Standard Deviation 9.1
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Occipital lobe
38.6 mL/cm^3
Standard Deviation 6.5
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Insula
63.3 mL/cm^3
Standard Deviation 9.0
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Frontal lobe
41.6 mL/cm^3
Standard Deviation 5.9
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Cingulate
58.3 mL/cm^3
Standard Deviation 8.6
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Parietal lobe
39.2 mL/cm^3
Standard Deviation 5.8
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Amygdala
89.8 mL/cm^3
Standard Deviation 15.2
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model)
Striatum
102.7 mL/cm^3
Standard Deviation 17.8

PRIMARY outcome

Timeframe: 1 week

The determination of the regional density and distribution of the I2BS in human brain of healthy volunteers. The output parameter used to determine this will be derived from the most appropriate PET pharmacokinetic model for this ligand in human e.g. Total Volume of Distribution (VT) or Binding Potential (BP). Regional time-activity data were generated from arterial plasma input functions corrected for metabolites using the most appropriate model to derive the outcome measure VT (regional distribution volume). All image processing and kinetic analyses were performed in MIAKAT. The Akaike model selection criteria were used to determine the most appropriate model to describe these data. The calculated criteria for the three main models are: one-tissue (1TCM) and two-tissue (2TCM) compartmental models, and multilinear analysis model (MA).

Outcome measures

Outcome measures
Measure
Healthy Volunteers
n=18 Participants
\[11C\]BU99008: Baseline Scan, Test-ReTest or Dosimetry Idazoxan: Idazoxan block of \[11C\]BU99008 Isocarboxazid: Isocarboxazid block of \[11C\]BU99008
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Whole Brain
48.8 mL/cm^3
Standard Deviation 7.9
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Frontal lobe
45.7 mL/cm^3
Standard Deviation 7.9
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Cerebellum
41.9 mL/cm^3
Standard Deviation 6.9
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Brain stem
66.4 mL/cm^3
Standard Deviation 10.1
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Occipital lobe
42.7 mL/cm^3
Standard Deviation 8.6
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Insula
67.7 mL/cm^3
Standard Deviation 11.8
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Cingulate
62.2 mL/cm^3
Standard Deviation 9.7
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Parietal lobe
43.6 mL/cm^3
Standard Deviation 8.7
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Amygdala
94.6 mL/cm^3
Standard Deviation 20.3
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Hippocampus
77.7 mL/cm^3
Standard Deviation 24.2
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Striatum
105.7 mL/cm^3
Standard Deviation 21.0
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (2TCM Model)
Thalamus
80.0 mL/cm^3
Standard Deviation 14.1

PRIMARY outcome

Timeframe: 1 week

The determination of the regional density and distribution of the I2BS in human brain of healthy volunteers. The output parameter used to determine this will be derived from the most appropriate PET pharmacokinetic model for this ligand in human e.g. Total Volume of Distribution (VT) or Binding Potential (BP). Regional time-activity data were generated from arterial plasma input functions corrected for metabolites using the most appropriate model to derive the outcome measure VT (regional distribution volume). All image processing and kinetic analyses were performed in MIAKAT. The Akaike model selection criteria were used to determine the most appropriate model to describe these data. The calculated criteria for the three main models are: one-tissue (1TCM) and two-tissue (2TCM) compartmental models, and multilinear analysis model (MA).

Outcome measures

Outcome measures
Measure
Healthy Volunteers
n=18 Participants
\[11C\]BU99008: Baseline Scan, Test-ReTest or Dosimetry Idazoxan: Idazoxan block of \[11C\]BU99008 Isocarboxazid: Isocarboxazid block of \[11C\]BU99008
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Striatum
104.2 mL/cm^3
Standard Deviation 17.6
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Whole Brain
44.8 mL/cm^3
Standard Deviation 6.1
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Cerebellum
39.6 mL/cm^3
Standard Deviation 6.2
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Brain stem
63.2 mL/cm^3
Standard Deviation 9.2
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Occipital lobe
38.8 mL/cm^3
Standard Deviation 6.5
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Insula
63.9 mL/cm^3
Standard Deviation 9.1
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Frontal lobe
42.0 mL/cm^3
Standard Deviation 5.9
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Cingulate
58.8 mL/cm^3
Standard Deviation 8.6
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Parietal lobe
39.5 mL/cm^3
Standard Deviation 5.9
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Amygdala
91.1 mL/cm^3
Standard Deviation 15.1
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Hippocampus
69.1 mL/cm^3
Standard Deviation 11.5
Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (MA Model)
Thalamus
76.0 mL/cm^3
Standard Deviation 11.1

SECONDARY outcome

Timeframe: 1 year

To evaluate the variability in the regional brain expression of I2BS within and between subjects using coefficient of variability (%COV). The %COV will be obtained from the most appropriate I2BS expression measures either Total Volume of Distribution (VT) or Binding Potential (BP).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

To evaluate the distribution of I2BS in the human body. The output parameter used to determine this will be derived from the most appropriate PET pharmacokinetic model for this ligand in human e.g. Total Volume of Distribution (VT) or Binding Potential (BP).

Outcome measures

Outcome data not reported

Adverse Events

Healthy Volunteers

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

Dr Robin J Tyacke

Imperial College London

Phone: (0)20 7594 7096

Results disclosure agreements

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