Normal PhysiologyPhase 1NCT03326245
Dopaminergic Modulation of Brain Activation Using Simultaneous PET/Pharmacological MRI
A Phase 1 study testing Methylphenidate Pill and Intravenous methylphenidate in people with Normal Physiology, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial summary
Background: Dopamine (DA) is a chemical signal in the brain linked to learning, memory, and habits. Stimulant drugs like methylphenidate can increase DA in the brain. Researchers want to measure DA with and without this drug. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Normal Physiology
- What is being tested?
- Methylphenidate Pill and Intravenous methylphenidate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jan 2018to 8 Feb 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy Volunteer Participants
- Males or females between 18 and 55 years of age.
- Ability to provide written informed consent.
- Willing to abstain from drug use on scheduled testing days.
- Have or had any prior experience with alcohol use or stimulant drugs including cocaine, methylphenidate, amphetamine or methamphetamine, diet pills (prescription or over the counter), caffeine, and others but did not have a substance use disorder.
Who cannot join
- Pregnant or breastfeeding. Females of childbearing potential must have negative urine pregnancy test and not be currently breastfeeding. Postmenopausal or surgically sterile (tubal ligation or hysterectomy) females satisfy these criteria.
- Unwilling or unable to refrain from use within 24 hours of scheduled study procedures: psychoactive medications or medication that may affect study results (e.g., antibiotics (must finish course at least 24 hours prior to a scheduled procedure), antidiarrheal preparations, anti-inflammatory drugs [systemic corticosteroids are exclusionary], anti-nausea, cough/cold preparations) (self-report, medical history). The following medications are allowable for entry on this study: analgesics (non-narcotic); antacids; antiasthma agents that are not systemic corticosteroids; antifungal agents for topical use; antihistamines (non-sedating); H2-Blockers/proton pump inhibitors (PPI); laxatives. The use of antihyperlipidemics and/or diuretics are permitted if they have been taken for at least 1 month before procedure visits and dose has been stabilized. The episodic use of benzodiazepines such as alprazolam (Xanax), diazepam (Valium) and lorazepam (Ativan), will not exclude participants from this study unless they have been taken within the last 24 hours prior to the study.
- The following current chronically used medications are exclusionary from the study: stimulant or stimulant-like medications (amphetamine, methylphenidate, modafinil); analgesics containing narcotics; anorexics (sibutramine); antianginal agents; antiarrhythmics; antiasthma agents that are systemic corticosteroids; antibiotics; anticholinergics; anticoagulants; anticonvulsants; antidepressants; antidiarrheal preparations; antifungal agents (systemic); antihistamines (sedating); antihypertensives; anti-inflammatory drugs (systemic); antineoplastics; antiobesity; antipsychotics; antivirals (except for treatment of HSV with agents without CNS activity, e.g. acyclovir, ganciclovir, famciclovir, valacyclovir); anxiolytics (benzodiazepine or barbiturates); hormones (exceptions: thyroid hormone replacement, oral contraceptives, and estrogen replacement therapy); insulin; lithium; muscle relaxants; psychotropic drugs not otherwise specified (nos) including herbal products (no drugs with psychomotor effects or with anxiolytics, stimulant, antipsychotic, or sedative properties); sedatives/hypnotics. Note that nicotine and/or caffeine use will not exclude participants.
- Current or past Diagnostic and Statistical Manual (DSM)-IV or DSM-5 diagnosis of a psychiatric disorder as determined by history and clinical exam including substance use disorder (except for nicotine/caffeine), alcohol use disorder (or alcohol dependence, if assessed using DSM-IV) anxiety disorder or panic attacks. Past history of a mental disorder as defined by DSM-IV or DSM-5 will be excluded only if it required hospitalization (any length), or chronic medication management (more than 4 weeks), and that could impact brain function at the time of the study.
- Those with a binge drinking history every month continuously for the last 10 years will also be excluded. Binge drinkers are those who being female consume 4 or more drinks and males consume 5 or more drinks in one occasion at least once a month.
- Major medical problems that can impact brain function at the time of the scan (including but not limited to HIV; glaucoma, central nervous system including seizures and psychosis; cardiovascular including hypertension and arrhythmias; metabolic, autoimmune, endocrine) as determined by history and clinical exam.
Show all 19Show fewer
- Any clinically significant laboratory finding as determined during the screening procedures.
- Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that, with the exposure from this study, would exceed NIH annual research limits.
- Head trauma with loss of consciousness for more than 30 minutes.
- Presence of ferromagnetic objects in the body that are contraindicated for PET/phMRI of the head (pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments), fear of enclosed spaces, or other standard contraindication to MRI/magnetic resonance spectroscopy (MRS) (self-report checklist).
- Cannot lie comfortably flat on back for up to 2 hours in the PET/phMRI scanner.
- Body weight > 204 kg (> 450 lbs).
- Allergy to methylphenidate.
- Clinically significant EKG abnormalities. Clinically significant findings on EKG will be assessed by the Medical Advisory Investigator on the study or through a cardiology consult. EKG reviews are documented in Clinical Research Information System (CRIS).
- History of glaucoma as determined by medical history.
- NIH employees who are study investigators, as well as their superiors, subordinates and immediate family members (adult children, spouses, parents, siblings).
- Non-English speakers (must also be able to read and comprehend English).
- Subjects will not be excluded from enrollment in this study if their urine test is positive for drugs. However, if they test positive on scheduled study procedure days involving study imaging and neuropsychological testing, the procedures will be postponed and rescheduled. We will allow for up to 3 rescheduled study days that were the result of positive urine drug screens. If the drug test is positive on the third rescheduled visit, the participant will be withdrawn from the study. The intent of the research has no prospect of direct benefit to the subject. Therefore, we are excluding non-English speakers in this research study since it includes the administration of questionnaires, surveys and assessments that are validated for English, although some are available in Spanish. In addition,
- our fMRI paradigms (particularly the Delay Discounting task) require that the subject be able to speak, read and comprehend English.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
Dopamine (DA) is a chemical signal in the brain linked to learning, memory, and habits. Stimulant drugs like methylphenidate can increase DA in the brain. Researchers want to measure DA with and without this drug. They want to learn how methylphenidate and brain dopamine affect body responses, mood, and thinking.
Read more
Objective:
To better understand the role of dopamine in the brain and the effects of methylphenidate.
Eligibility:
Adults ages 18-55 who have used alcohol or stimulant drugs but have no drug dependence.
Design:
Participants will be screened with:
- Physical exam
- Question about medical, psychiatric, and alcohol and drug use history
- Questions to see if it s safe to have a PET/MRI scan
- Blood and urine tests
- Breath test for alcohol
Participants will have 3 or 4 study visits. At each visit they will have:
- Urine and breath tested for alcohol and drugs
- A thin plastic tube (catheter) inserted in each arm by needle
- A small amount of radioactive chemical injected through the catheter.
- PET/MRI scan. Participants will lie still on a table that slides in and out of a metal cylinder surrounded by a strong magnetic field. Their vital signs will be monitored. They will get earmuffs for loud noises. Before the scan, participants will get the study drug or placebo through the catheter. They may also get a sugar pill (placebo). They will get a small meal and have blood drawn.
- Tests of memory, attention, and thinking.
Participants will wear an activity monitor on the wrist for one week.
Read the detailed description
Objectives: The overarching goal of this study is to assess the dynamic association between dopamine (DA) D2 receptor (D2R) occupancy measured by positron emission tomography (PET) with [11C]raclopride and brain activity inferred by pharmacological magnetic resonance imaging (phMRI) in the human brain, and to assess the relative sensitivity and specificity of the neurovascular coupling for slow (oral) versus rapid (intravenous, IV) stimulant methylphenidate (MP) delivery. Secondary objectives are to assess the associations between behavioral measures (heart and respiration rates and blood pressure, motor and sleep parameters, and neuropsychological testing variables), D2R occupancy and fMRI signals.
Study population: 10 healthy males and 10 healthy females 18-55 years old will be included. Test-retest reproducibility studies will be carried out in 5 participants.
Design: Double-blind. Participants will undergo simultaneous PET/phMRI, to evaluate dynamic changes in D2R occupancy by DA with [11C]raclopride and in blood-oxygenation-level dependent (BOLD) signals, under MP or placebo (PL). The participants will be scanned on 3 different occasions: 1) oral-MP (60 mg) and iv PL (3 cc saline), 2) oral-PL and iv-MP (0.25 mg/kg in 3 cc sterile water) and 3) oral PL and iv PL, which will be carried in different study days with at least 48 hours between them and their order will be randomized across subjects. Participants and researchers will be blind to the nature of the stimulant drug (MP/PL).
Outcome parameters: The scale factor between the distribution volume ratio (DVR) and the BOLD signal in the dorsal and ventral striatum for the slow and fast MP challenges.
- Conditions
- Normal Physiology
- Being tested
- Methylphenidate Pill, Oral Placebo, Intravenous Placebo, Intravenous methylphenidate
- Keywords
- Pharmacological MRI, C-11 Raclopride, PET Imaging, Neuropsychological Testing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylphenidate PillDrug
Also called Ritalin
Oral methylphenidate (60 mg) given 30 minutes prior to bolus [11C]raclopride
Oral PlaceboDrug
Oral PL will be given 30 minutes prior to bolus [11C]raclopride injection
Intravenous PlaceboDrug
Intravenous Placebo given 30 minutes post bolus injection of [11C]raclopride.
Intravenous methylphenidateDrug
Intravenous methylphenidate 0.25 mg/kg in 3ml sterile saline given 30 minutes post bolus injection of [11C]raclopride.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Oral methylphenidate followed by intravenous placebo | Active comparator | 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. Receives: Drug: Methylphenidate Pill; Drug: Intravenous Placebo |
| Arm B: Oral placebo followed by intravenous methylphenidate | Active comparator | 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. Receives: Drug: Oral Placebo; Drug: Intravenous methylphenidate |
| Arm C: Oral placebo followed by intravenous placebo | Placebo comparator | 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. Receives: Drug: Oral Placebo; Drug: Intravenous Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Standardized Uptake Value Ratio (SUVR) for [11C]Raclopride in Putamen
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.
Measured: 60 min after [11C]raclopride injection
Percent BOLD Signal Change in the Anterior Cingulum
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.
Measured: From 0 to 90 minutes after [11C]raclopride injection
The Temporal Correlation Between BOLD(t) and SUVR(t) Change
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.
Measured: From 0 to 90 minutes after [11C]raclopride injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2017
- Study start29 Jan 2018
- Primary completion13 Dec 2021
- Study completion8 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Normal PhysiologyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Dardo G Tomasi, Ph.D., Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03326245
- Sponsor's protocol ID
- 170178
- Other IDs
- 17-AA-0178
- Status last verified
- 27 Oct 2023
- First submitted
- 28 Oct 2017
- Last updated
- 28 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: .Data is analyzed by subject group and not on an individual basis.
Publications
Manza P, Tomasi D, Shokri-Kojori E, Zhang R, Kroll D, Feldman D, McPherson K, Biesecker C, Dennis E, Johnson A, Yuan K, Wang WT, Yonga MV, Wang GJ, Volkow ND. Neural circuit selective for fast but not slow dopamine increases in drug reward. Nat Commun. 2023 Nov 8;14(1):6408. doi: 10.1038/s41467-023-41972-6.
PubMed 37938560Manza P, Tomasi D, Vines L, Sotelo D, Yonga MV, Wang GJ, Volkow ND. Brain connectivity changes to fast versus slow dopamine increases. Neuropsychopharmacology. 2024 May;49(6):924-932. doi: 10.1038/s41386-024-01803-8. Epub 2024 Feb 7.
PubMed 38326458Tomasi D, Manza P, Yan W, Shokri-Kojori E, Demiral SB, Yonga MV, McPherson K, Biesecker C, Dennis E, Johnson A, Zhang R, Wang GJ, Volkow ND. Examining the role of dopamine in methylphenidate's effects on resting brain function. Proc Natl Acad Sci U S A. 2023 Dec 26;120(52):e2314596120. doi: 10.1073/pnas.2314596120. Epub 2023 Dec 18.
PubMed 38109535Tomasi D, Manza P, Logan J, Shokri-Kojori E, Yonga MV, Kroll D, Feldman D, McPherson K, Biesecker C, Dennis E, Johnson A, Yuan K, Wang WT, Butman JA, Wang GJ, Volkow ND. Time-varying SUVr reflects the dynamics of dopamine increases during methylphenidate challenges in humans. Commun Biol. 2023 Feb 10;6(1):166. doi: 10.1038/s42003-023-04545-3.
PubMed 36765261
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dopaminergic Modulation of Brain Activation Using Simultaneous PET/Pharmacological MRI
- ClinicalTrials.gov ID
- NCT03326245
- Acronym / sponsor ID
- 170178
- Conditions
- Normal Physiology
- Keywords
- Pharmacological MRI, C-11 Raclopride, PET Imaging, Neuropsychological Testing
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- 29 Jan 2018 (actual)
- Primary completion
- 13 Dec 2021 (actual)
- Study completion
- 8 Feb 2024 (actual)
- First posted
- 31 Oct 2017 (actual)
- Results
- Posted 28 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Dopamine (DA) is a chemical signal in the brain linked to learning, memory, and habits. Stimulant drugs like methylphenidate can increase DA in the brain. Researchers want to measure DA with and without this drug. They want to learn how methylphenidate and brain dopamine affect body responses, mood, and thinking.
Objective:
To better understand the role of dopamine in the brain and the effects of methylphenidate.
Eligibility:
Adults ages 18-55 who have used alcohol or stimulant drugs but have no drug dependence.
Design:
Participants will be screened with:
- Physical exam
- Question about medical, psychiatric, and alcohol and drug use history
- Questions to see if it s safe to have a PET/MRI scan
- Blood and urine tests
- Breath test for alcohol
Participants will have 3 or 4 study visits. At each visit they will have:
- Urine and breath tested for alcohol and drugs
- A thin plastic tube (catheter) inserted in each arm by needle
- A small amount of radioactive chemical injected through the catheter.
- PET/MRI scan. Participants will lie still on a table that slides in and out of a metal cylinder surrounded by a strong magnetic field. Their vital signs will be monitored. They will get earmuffs for loud noises. Before the scan, participants will get the study drug or placebo through the catheter. They may also get a sugar pill (placebo). They will get a small meal and have blood drawn.
- Tests of memory, attention, and thinking.
Participants will wear an activity monitor on the wrist for one week.
Detailed description
Objectives: The overarching goal of this study is to assess the dynamic association between dopamine (DA) D2 receptor (D2R) occupancy measured by positron emission tomography (PET) with [11C]raclopride and brain activity inferred by pharmacological magnetic resonance imaging (phMRI) in the human brain, and to assess the relative sensitivity and specificity of the neurovascular coupling for slow (oral) versus rapid (intravenous, IV) stimulant methylphenidate (MP) delivery. Secondary objectives are to assess the associations between behavioral measures (heart and respiration rates and blood pressure, motor and sleep parameters, and neuropsychological testing variables), D2R occupancy and fMRI signals.
Study population: 10 healthy males and 10 healthy females 18-55 years old will be included. Test-retest reproducibility studies will be carried out in 5 participants.
Design: Double-blind. Participants will undergo simultaneous PET/phMRI, to evaluate dynamic changes in D2R occupancy by DA with [11C]raclopride and in blood-oxygenation-level dependent (BOLD) signals, under MP or placebo (PL). The participants will be scanned on 3 different occasions: 1) oral-MP (60 mg) and iv PL (3 cc saline), 2) oral-PL and iv-MP (0.25 mg/kg in 3 cc sterile water) and 3) oral PL and iv PL, which will be carried in different study days with at least 48 hours between them and their order will be randomized across subjects. Participants and researchers will be blind to the nature of the stimulant drug (MP/PL).
Outcome parameters: The scale factor between the distribution volume ratio (DVR) and the BOLD signal in the dorsal and ventral striatum for the slow and fast MP challenges.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: Oral methylphenidate followed by intravenous placebo | Active comparator | Drug: Methylphenidate Pill, Drug: Intravenous PlaceboHealthy 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 | Active comparator | Drug: Oral Placebo, Drug: Intravenous methylphenidateHealthy 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 | Placebo comparator | Drug: Oral Placebo, Drug: Intravenous PlaceboHealthy 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy Volunteer Participants
- Males or females between 18 and 55 years of age.
- Ability to provide written informed consent.
- Willing to abstain from drug use on scheduled testing days.
- Have or had any prior experience with alcohol use or stimulant drugs including cocaine, methylphenidate, amphetamine or methamphetamine, diet pills (prescription or over the counter), caffeine, and others but did not have a substance use disorder.
Key exclusion criteria (19 listed)
- Pregnant or breastfeeding. Females of childbearing potential must have negative urine pregnancy test and not be currently breastfeeding. Postmenopausal or surgically sterile (tubal ligation or hysterectomy) females satisfy these criteria.
- Unwilling or unable to refrain from use within 24 hours of scheduled study procedures: psychoactive medications or medication that may affect study results (e.g., antibiotics (must finish course at least 24 hours prior to a scheduled procedure), antidiarrheal preparations, anti-inflammatory drugs [systemic corticosteroids are exclusionary], anti-nausea, cough/cold preparations) (self-report, medical history). The following medications are allowable for entry on this study: analgesics (non-narcotic); antacids; antiasthma agents that are not systemic corticosteroids; antifungal agents for topical use; antihistamines (non-sedating); H2-Blockers/proton pump inhibitors (PPI); laxatives. The use of antihyperlipidemics and/or diuretics are permitted if they have been taken for at least 1 month before procedure visits and dose has been stabilized. The episodic use of benzodiazepines such as alprazolam (Xanax), diazepam (Valium) and lorazepam (Ativan), will not exclude participants from this study unless they have been taken within the last 24 hours prior to the study.
- The following current chronically used medications are exclusionary from the study: stimulant or stimulant-like medications (amphetamine, methylphenidate, modafinil); analgesics containing narcotics; anorexics (sibutramine); antianginal agents; antiarrhythmics; antiasthma agents that are systemic corticosteroids; antibiotics; anticholinergics; anticoagulants; anticonvulsants; antidepressants; antidiarrheal preparations; antifungal agents (systemic); antihistamines (sedating); antihypertensives; anti-inflammatory drugs (systemic); antineoplastics; antiobesity; antipsychotics; antivirals (except for treatment of HSV with agents without CNS activity, e.g. acyclovir, ganciclovir, famciclovir, valacyclovir); anxiolytics (benzodiazepine or barbiturates); hormones (exceptions: thyroid hormone replacement, oral contraceptives, and estrogen replacement therapy); insulin; lithium; muscle relaxants; psychotropic drugs not otherwise specified (nos) including herbal products (no drugs with psychomotor effects or with anxiolytics, stimulant, antipsychotic, or sedative properties); sedatives/hypnotics. Note that nicotine and/or caffeine use will not exclude participants.
- Current or past Diagnostic and Statistical Manual (DSM)-IV or DSM-5 diagnosis of a psychiatric disorder as determined by history and clinical exam including substance use disorder (except for nicotine/caffeine), alcohol use disorder (or alcohol dependence, if assessed using DSM-IV) anxiety disorder or panic attacks. Past history of a mental disorder as defined by DSM-IV or DSM-5 will be excluded only if it required hospitalization (any length), or chronic medication management (more than 4 weeks), and that could impact brain function at the time of the study.
- Those with a binge drinking history every month continuously for the last 10 years will also be excluded. Binge drinkers are those who being female consume 4 or more drinks and males consume 5 or more drinks in one occasion at least once a month.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylphenidate PillAlso: RitalinOral methylphenidate (60 mg) given 30 minutes prior to bolus [11C]raclopride | Drug | Arm A: Oral methylphenidate followed by intravenous placebo |
| Oral PlaceboOral PL will be given 30 minutes prior to bolus [11C]raclopride injection | Drug | Arm B: Oral placebo followed by intravenous methylphenidate, Arm C: Oral placebo followed by intravenous placebo |
| Intravenous PlaceboIntravenous Placebo given 30 minutes post bolus injection of [11C]raclopride. | Drug | Arm A: Oral methylphenidate followed by intravenous placebo, Arm C: Oral placebo followed by intravenous placebo |
| Intravenous methylphenidateIntravenous methylphenidate 0.25 mg/kg in 3ml sterile saline given 30 minutes post bolus injection of [11C]raclopride. | Drug | Arm B: Oral placebo followed by intravenous methylphenidate |
Primary outcome
The Standardized Uptake Value Ratio (SUVR) for [11C]Raclopride in Putamen
Time frame: 60 min after [11C]raclopride injection
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.
Percent BOLD Signal Change in the Anterior Cingulum
Time frame: From 0 to 90 minutes after [11C]raclopride injection
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.
The Temporal Correlation Between BOLD(t) and SUVR(t) Change
Time frame: From 0 to 90 minutes after [11C]raclopride injection
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37938560Manza P, Tomasi D, Shokri-Kojori E, Zhang R, Kroll D, Feldman D, McPherson K, Biesecker C, Dennis E, Johnson A, Yuan K, Wang WT, Yonga MV, Wang GJ, Volkow ND. Neural circuit selective for fast but not slow dopamine increases in drug reward. Nat Commun. 2023 Nov 8;14(1):6408. doi: 10.1038/s41467-023-41972-6.
- Results publication: PubMed 38326458Manza P, Tomasi D, Vines L, Sotelo D, Yonga MV, Wang GJ, Volkow ND. Brain connectivity changes to fast versus slow dopamine increases. Neuropsychopharmacology. 2024 May;49(6):924-932. doi: 10.1038/s41386-024-01803-8. Epub 2024 Feb 7.
- Results publication: PubMed 38109535Tomasi D, Manza P, Yan W, Shokri-Kojori E, Demiral SB, Yonga MV, McPherson K, Biesecker C, Dennis E, Johnson A, Zhang R, Wang GJ, Volkow ND. Examining the role of dopamine in methylphenidate's effects on resting brain function. Proc Natl Acad Sci U S A. 2023 Dec 26;120(52):e2314596120. doi: 10.1073/pnas.2314596120. Epub 2023 Dec 18.
- Results publication: PubMed 36765261Tomasi D, Manza P, Logan J, Shokri-Kojori E, Yonga MV, Kroll D, Feldman D, McPherson K, Biesecker C, Dennis E, Johnson A, Yuan K, Wang WT, Butman JA, Wang GJ, Volkow ND. Time-varying SUVr reflects the dynamics of dopamine increases during methylphenidate challenges in humans. Commun Biol. 2023 Feb 10;6(1):166. doi: 10.1038/s42003-023-04545-3.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. .Data is analyzed by subject group and not on an individual basis.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dardo G Tomasi, Ph.D. principal investigator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Methylphenidate Pill and Intravenous methylphenidate in people with Normal Physiology, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Standardized Uptake Value Ratio (SUVR) for [11C]Raclopride in Putamen (time frame: 60 min after [11C]raclopride injection). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03326245, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2024.