Trial Outcomes & Findings for Dopaminergic Modulation of Brain Activation Using Simultaneous PET/Pharmacological MRI (NCT NCT03326245)

Last Updated: 2024-05-28

Results Overview

Participants underwent brain positron emission tomography (PET) scan with \[11C\]raclopride. The SUVR is calculated by dividing the standardized uptake value in the putamen, target region, by the standardized uptake value in the cerebellum, the reference region. This ratio normalizes the uptake values and allows for comparisons between individuals or across different imaging sessions.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

60 min after [11C]raclopride injection

Results posted on

2024-05-28

Participant Flow

Three participants withdrew from the study prior to randomization

Participant milestones

Participant milestones
Measure	Arm A: Oral Methylphenidate Followed by Intravenous Placebo Healthy participants receive methylphenidate 60mg orally given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms B and C in different study days with at least 48 hours between visits.	Arm B: Oral Placebo Followed by Intravenous Methylphenidate Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous methylphenidate 0.25 mg/kg in 3ml sterile water given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms A and C in different study days with at least 48 hours between visits.	Arm C: Oral Placebo Followed by Intravenous Placebo Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms A and B in different study days with at least 48 hours between visits.
Visit Day A (First Intervention) STARTED	8	7	7
Visit Day A (First Intervention) COMPLETED	8	7	7
Visit Day A (First Intervention) NOT COMPLETED	0	0	0
Visit Day B (Second Intervention) STARTED	8	7	7
Visit Day B (Second Intervention) Randomized to Study Arm A	0	4	3
Visit Day B (Second Intervention) Randomized to Study Arm B	4	0	4
Visit Day B (Second Intervention) Randomized to Study Arm C	4	3	0
Visit Day B (Second Intervention) COMPLETED	8	7	7
Visit Day B (Second Intervention) NOT COMPLETED	0	0	0
Visit Day C (Third Intervention) STARTED	8	7	5
Visit Day C (Third Intervention) Randomized to Study Arm A	0	3	4
Visit Day C (Third Intervention) Randomized to Study Arm B	4	0	1
Visit Day C (Third Intervention) Randomized to Study Arm C	4	4	0
Visit Day C (Third Intervention) COMPLETED	8	7	5
Visit Day C (Third Intervention) NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dopaminergic Modulation of Brain Activation Using Simultaneous PET/Pharmacological MRI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Oral Methylphenidate Followed by Intravenous Placebo n=8 Participants Healthy participants receive methylphenidate 60mg orally given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection.	Arm B: Oral Placebo Followed by Intravenous Methylphenidate n=7 Participants Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous methylphenidate 0.25 mg/kg in 3ml sterile water given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection.	Arm C: Oral Placebo Followed by Intravenous Placebo n=7 Participants Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection.	Total n=22 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	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=99 Participants	7 Participants n=107 Participants	7 Participants n=206 Participants	22 Participants n=7 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Sex: Female, Male Female	4 Participants n=99 Participants	3 Participants n=107 Participants	2 Participants n=206 Participants	9 Participants n=7 Participants
Sex: Female, Male Male	4 Participants n=99 Participants	4 Participants n=107 Participants	5 Participants n=206 Participants	13 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=99 Participants	7 Participants n=107 Participants	6 Participants n=206 Participants	20 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	2 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 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	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants	5 Participants n=107 Participants	3 Participants n=206 Participants	10 Participants n=7 Participants
Race (NIH/OMB) White	4 Participants n=99 Participants	0 Participants n=107 Participants	3 Participants n=206 Participants	7 Participants n=7 Participants
Race (NIH/OMB) More than one race	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants

PRIMARY outcome

Timeframe: 60 min after [11C]raclopride injection

Population: All participants who received \[11C\]raclopride injection during the PET scans and completed all three arms of the study.

Outcome measures

Outcome measures
Measure	Arm A: Oral Methylphenidate Followed by Intravenous Placebo Placebo n=20 Participants Healthy participants receive methylphenidate 60mg orally given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms B and C in different study days with at least 48 hours between visits.	Arm B: Oral Placebo Followed by Intravenous Methylphenidate n=20 Participants Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous methylphenidate 0.25 mg/kg in 3ml sterile water given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms A and C in different study days with at least 48 hours between visits.	Arm C: Oral Placebo Followed by Intravenous Placebo n=20 Participants Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms A and B in different study days with at least 48 hours between visits.
The Standardized Uptake Value Ratio (SUVR) for [11C]Raclopride in Putamen	4.49 SUV Ratio (SUVR) Standard Deviation 0.39	4.39 SUV Ratio (SUVR) Standard Deviation 0.45	4.87 SUV Ratio (SUVR) Standard Deviation 0.46

PRIMARY outcome

Timeframe: From 0 to 90 minutes after [11C]raclopride injection

Population: All participants who received \[11C\]raclopride injection during the PET scans and completed all three arms of the study.

The blood-oxygen-level-dependent (BOLD) signal was estimated as the fitted amplitude to the dynamic standardized uptake value ratio (SUVR) change in response to the methylphenidate challenges.

Outcome measures

Outcome measures
Measure	Arm A: Oral Methylphenidate Followed by Intravenous Placebo Placebo n=20 Participants Healthy participants receive methylphenidate 60mg orally given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms B and C in different study days with at least 48 hours between visits.	Arm B: Oral Placebo Followed by Intravenous Methylphenidate n=20 Participants Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous methylphenidate 0.25 mg/kg in 3ml sterile water given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms A and C in different study days with at least 48 hours between visits.	Arm C: Oral Placebo Followed by Intravenous Placebo n=20 Participants Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms A and B in different study days with at least 48 hours between visits.
Percent BOLD Signal Change in the Anterior Cingulum	-0.13 percentage signal change Standard Deviation 0.28	1.210 percentage signal change Standard Deviation 0.620	-0.001 percentage signal change Standard Deviation 0.460

PRIMARY outcome

Timeframe: From 0 to 90 minutes after [11C]raclopride injection

Population: Analysis include all 20 participants who completed the study and received methylphenidate orally and intravenously as pre-specified in the protocol

The Pearson correlation between the temporal dynamics of the blood-oxygen-level-dependent (BOLD) signal in anterior cingulum and the standardized uptake value ratio (SUVR) change in putamen measures changes in the neurovascular coupling induced by methylphenidate.

Outcome measures

Outcome measures
Measure	Arm A: Oral Methylphenidate Followed by Intravenous Placebo Placebo n=20 Participants Healthy participants receive methylphenidate 60mg orally given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms B and C in different study days with at least 48 hours between visits.	Arm B: Oral Placebo Followed by Intravenous Methylphenidate n=20 Participants Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous methylphenidate 0.25 mg/kg in 3ml sterile water given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms A and C in different study days with at least 48 hours between visits.	Arm C: Oral Placebo Followed by Intravenous Placebo Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection. Participants were subsequently randomized across study arms A and B in different study days with at least 48 hours between visits.
The Temporal Correlation Between BOLD(t) and SUVR(t) Change	.023 correlation coefficient (r) Standard Deviation .376	.556 correlation coefficient (r) Standard Deviation .219	—

Adverse Events

Arm A: Oral Methylphenidate Followed by Intravenous Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Arm B: Oral Placebo Followed by Intravenous Methylphenidate

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Arm C: Oral Placebo Followed by Intravenous Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Dardo Tomasi

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Phone: +1 301 496 1589

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A: Oral Methylphenidate Followed by Intravenous Placebo n=22 participants at risk Healthy participants receive methylphenidate 60mg orally given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection.	Arm B: Oral Placebo Followed by Intravenous Methylphenidate n=22 participants at risk Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous methylphenidate 0.25 mg/kg in 3ml sterile water given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection.	Arm C: Oral Placebo Followed by Intravenous Placebo n=22 participants at risk Healthy participants receive oral placebo given 30 minutes prior to bolus \[11C\]raclopride injection followed by intravenous placebo (3ml saline) given 30 minutes post bolus injection of \[11C\]raclopride. PET/phMRI scan (MRI and PET scan) was initiated at the start of the \[11C\]raclopride injection.
Cardiac disorders Palpitations	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Gastrointestinal disorders Nausea	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	9.1% 2/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
General disorders Feeling of relaxation	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	9.1% 2/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
General disorders Pain	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	9.1% 2/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Nervous system disorders Agitation	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	13.6% 3/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Nervous system disorders Disturbance in attention	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Nervous system disorders Dizziness	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Nervous system disorders Headache	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Nervous system disorders Logorrhoea	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Nervous system disorders Restlessness	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Nervous system disorders Sensory disturbance	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Psychiatric disorders Anxiety	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	9.1% 2/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Psychiatric disorders Disturbance in sexual arousal	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Psychiatric disorders Euphoric mood	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit
Psychiatric disorders Paranoia	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	4.5% 1/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit	0.00% 0/22 • Participants were monitored over 4-6 clinic visits for up to 6 hours per clinic visit