PTSDEarly Phase 1NCT02021214
Effects of Methylphenidate (Ritalin®) on the Neural Basis of Anxiety
A Early Phase 1 study testing Methylphenidate in people with PTSD, run by University of California, San Diego at 1 site in United States.
Trial summary
In the present study, investigator will investigate the effects of methylphenidate (40 mg) on mPFC activity in healthy male volunteers during fear extinction using functional magnetic resonance imaging (fMRI). Additionally, investigators will examine the effects of methylphenidate during aversive interoceptve arousal. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- PTSD
- What is being tested?
- Methylphenidate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Oct 2014
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male subjects, 18 to 40 years of age, inclusive.
- In good general health (as determined by medical history, blood pressure, and ECG), especially no findings (including concomitant medications) that would constitute contraindications for treatment with any of the study drugs.
- A weight of > 120 lbs (55 kg) and a BMI between 18 to 30 kg/m2, inclusive.
- Participants must be willing to drink only alcohol-free liquids and no xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) the day before and during the study day.
- Subjects able to participate and willing to give written informed consent and to comply with the study restrictions.
Who cannot join
- History of any hematological, hepatic, respiratory, cardiovascular (including structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease or myocardial infarction), renal or CNS disease (including seizures), gallbladder removal or other medical or surgical condition that could alter the absorption, metabolism or elimination of drugs.
- Family history of sudden death or ventricular arrhythmia.
- Any major illness (as judged by the study physician) within 1 month prior to first dose.
- Current or history of any psychiatric disorder, marked anxiety, tension and agitation.
- History of glaucoma.
- History (including family history) of motor tic or diagnosis of Tourette's syndrome.
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- History of psychotropic medicine and/or alcohol dependence.
- Active suicidal ideation, history of suicidal behavior, or otherwise considered at high suicidal risk by trained study staff using the C-SSRS.
- Positive urine toxicology (drugs of abuse as determined by a positive urine test) at screening and before each drug administration.
- Use of any medications or herbal remedies, including psychotropic medicines and regular sleep medications, taken within 14 days or 6 times the elimination half-life of the medication (whichever is longer) prior to the first dose and throughout the study, with the exception of acetaminophen for minor pains, occasional use of sleeping medication as long as it is not taken the evening prior to a visit, medications explicitly approved by the investigator and the sponsor.
- Past intolerance (including allergic) to any of the study medications or components thereof.
- Supine systolic blood pressure (BP) >140 or >90 mmHg, diastolic BP <90 mmHg or <50 mmHg (mean of two measurements at screening) and current or past history of clinically significant hypertension.
- Current smoker (> 10 cigarettes/day); habitual caffeine consumption of more than 400 mg/d (approximately 4 cups of coffee or equivalent).
- QTcF > 450 msec based on the average interval on triplicate ECGs. Notable resting bradycardia (mean HR < 45 bpm) or notable resting tachycardia (mean HR > 90 bpm).
- Contraindication to magnetic resonance imaging.
- Participation in a clinical trial with an investigational drug or a device within 30 days prior to dosing in the first period.
- Volunteers who do not have sufficient command of the English language, or who have any other impairment that would prevent them from reading and understanding the informed consent form(s) and completing the study procedures including clinical testing.
- Any other reason why, per study physician, the subject should not participate in this study, including concomitant disease or condition that could interfere with, or for which the study drug might interfere with, the conduct of the study, or that would, in the opinion of the principal investigator, pose an unacceptable risk to the subject in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSD Psychiatry Clinical Research
San Diego, California, 92037
About this study
Official title: Effects of Methylphenidate (Ritalin®) on the Neural Basis of Anxiety: a Placebo-controlled fMRI Study in Healthy Male Subjects
In the present study, investigator will investigate the effects of methylphenidate (40 mg) on mPFC activity in healthy male volunteers during fear extinction using functional magnetic resonance imaging (fMRI). Additionally, investigators will examine the effects of methylphenidate during aversive interoceptve arousal. The present study will help to identify brain structures and networks involved in anxiety and will give insights for methylphenidate as a possible adjunct to behavioral therapy for patients with anxiety disorders. Further, this study may provide important information about the possible use of fMRI to help the development of drugs for the treatment of anxiety disorders.
Read the detailed description
Posttraumatic stress disorder (PTSD) affects 5-10% of the general U.S. population at some point during their lifetime; however, the prevalence in much higher among certain subgroups, including active duty military personnel and veterans. Pharmacotherapy of PTSD has made little headway on the past two decades. Methylphenidate (Ritalin®) is a stimulant drug that amplifies dopaminergic and noradrenergic signaling in the brain. Dopamine and norepinephrine are thought to play a critical role during fear extinction by moderating medial prefrontal cortex (mPFC) activity. The magnitude of mPFC activity seems to crucially affect the degree of fear extinction. The model of fear extinction is one approach to conceptualize PTSD. Thereby a previously neutral stimulus is paired with a highly aversive unconditioned stimulus. Fear extinction refers to the decrement in that conditioned fear responses that occur with repeated presentation of the conditioned neutral fear stimulus without the aversive stimulus. While preclinical data suggest that a single dose of methylphenidate enhances fear extinction, it is less clear how methylphenidate affects fear extinction in humans. However, exposing PTSD patients to new therapies is difficult. In the present study, investigator will investigate the effects of methylphenidate (40 mg) on mPFC activity in healthy male volunteers during fear extinction using functional magnetic resonance imaging (fMRI). Additionally, investigators will examine the effects of methylphenidate during aversive interoceptve arousal. The present study will help to identify brain structures and networks involved in anxiety and will give insights for methylphenidate as a possible adjunct to behavioral therapy for patients with anxiety disorders. Further, this study may provide important information about the possible use of fMRI to help the development of drugs for the treatment of anxiety disorders.
- Conditions
- PTSD
- Being tested
- Methylphenidate, Placebo
- Keywords
- Methylphenidate, Fear extinction, fMRI, mPFC
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylphenidateDrug
Also called Ritalin
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate/Placebo | Experimental | 40 mg Methylphenidate, per os, single dose Placebo, single dose Receives: Drug: Methylphenidate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in blood oxygenation level-dependent BOLD signal responses
Methylphenidate-induced changes in BOLD signal responses in brain regions relevant in fear disorders (e.g. amygdala, insula, and prefrontal cortex) during a fear extinction task compared to placebo.
Measured: 6 hours
Secondary outcomes (3)
Changes in BOLD signal responses
Methylphenidate induced changes in BOLD signal responses in regions implicated in emotional processing while anticipating a positive interoceptive stimulus compared to placebo.
Measured: 6 hours
Changes in skin conductance response
Changes compared to placebo in skin conductance respo during a fear extinction task
Measured: 6 hours
Latency and accuracy during a interoceptive stimulus task
This task aims to examine the participants' response to an aversive interoceptive stimulus. Individuals will perform a simple continuous performance task during the paradigm. Subjects are asked to press one of three buttons to rate the images on the screen as either 'dislike', 'neutral' or 'like'. Both accuracy and response latency (ms) will be recorded to determine effects of anticipation and stimulus presentation
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2013 (estimated)
- Study startMar 2014
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTSDStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Double-blind, cross-over design with two drug conditions. Drug conditions are placebo and methylphenidate 40 mg. Order will be balanced and pseudo-random.
- Masking
- Double blind
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martin P Paulus, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02021214
- Sponsor's protocol ID
- 131297
- Status last verified
- Feb 2020
- First submitted
- 9 Dec 2013
- Last updated
- 28 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Methylphenidate (Ritalin®) on the Neural Basis of Anxiety: a Placebo-controlled fMRI Study in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT02021214
- Acronym / sponsor ID
- 131297
- Conditions
- PTSD
- Keywords
- Methylphenidate, Fear extinction, fMRI, mPFC
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 27 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the present study, investigator will investigate the effects of methylphenidate (40 mg) on mPFC activity in healthy male volunteers during fear extinction using functional magnetic resonance imaging (fMRI). Additionally, investigators will examine the effects of methylphenidate during aversive interoceptve arousal. The present study will help to identify brain structures and networks involved in anxiety and will give insights for methylphenidate as a possible adjunct to behavioral therapy for patients with anxiety disorders. Further, this study may provide important information about the possible use of fMRI to help the development of drugs for the treatment of anxiety disorders.
Detailed description
Posttraumatic stress disorder (PTSD) affects 5-10% of the general U.S. population at some point during their lifetime; however, the prevalence in much higher among certain subgroups, including active duty military personnel and veterans. Pharmacotherapy of PTSD has made little headway on the past two decades. Methylphenidate (Ritalin®) is a stimulant drug that amplifies dopaminergic and noradrenergic signaling in the brain. Dopamine and norepinephrine are thought to play a critical role during fear extinction by moderating medial prefrontal cortex (mPFC) activity. The magnitude of mPFC activity seems to crucially affect the degree of fear extinction. The model of fear extinction is one approach to conceptualize PTSD. Thereby a previously neutral stimulus is paired with a highly aversive unconditioned stimulus. Fear extinction refers to the decrement in that conditioned fear responses that occur with repeated presentation of the conditioned neutral fear stimulus without the aversive stimulus. While preclinical data suggest that a single dose of methylphenidate enhances fear extinction, it is less clear how methylphenidate affects fear extinction in humans. However, exposing PTSD patients to new therapies is difficult. In the present study, investigator will investigate the effects of methylphenidate (40 mg) on mPFC activity in healthy male volunteers during fear extinction using functional magnetic resonance imaging (fMRI). Additionally, investigators will examine the effects of methylphenidate during aversive interoceptve arousal. The present study will help to identify brain structures and networks involved in anxiety and will give insights for methylphenidate as a possible adjunct to behavioral therapy for patients with anxiety disorders. Further, this study may provide important information about the possible use of fMRI to help the development of drugs for the treatment of anxiety disorders.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Double blind
- Number of arms
- 1
- Model description
- Double-blind, cross-over design with two drug conditions. Drug conditions are placebo and methylphenidate 40 mg. Order will be balanced and pseudo-random.
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate/Placebo | Experimental | Drug: Methylphenidate, Drug: Placebo40 mg Methylphenidate, per os, single dose Placebo, single dose |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy male subjects, 18 to 40 years of age, inclusive.
- In good general health (as determined by medical history, blood pressure, and ECG), especially no findings (including concomitant medications) that would constitute contraindications for treatment with any of the study drugs.
- A weight of > 120 lbs (55 kg) and a BMI between 18 to 30 kg/m2, inclusive.
- Participants must be willing to drink only alcohol-free liquids and no xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) the day before and during the study day.
- Subjects able to participate and willing to give written informed consent and to comply with the study restrictions.
Key exclusion criteria (18 listed)
- History of any hematological, hepatic, respiratory, cardiovascular (including structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease or myocardial infarction), renal or CNS disease (including seizures), gallbladder removal or other medical or surgical condition that could alter the absorption, metabolism or elimination of drugs.
- Family history of sudden death or ventricular arrhythmia.
- Any major illness (as judged by the study physician) within 1 month prior to first dose.
- Current or history of any psychiatric disorder, marked anxiety, tension and agitation.
- History of glaucoma.
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 |
|---|---|---|
| MethylphenidateAlso: Ritalin | Drug | Methylphenidate/Placebo |
| Placebo | Drug | Methylphenidate/Placebo |
Primary outcome
Changes in blood oxygenation level-dependent BOLD signal responses
Time frame: 6 hours
Methylphenidate-induced changes in BOLD signal responses in brain regions relevant in fear disorders (e.g. amygdala, insula, and prefrontal cortex) during a fear extinction task compared to placebo.
3 secondary outcomes
Changes in BOLD signal responses
Time frame: 6 hours
Changes in skin conductance response
Time frame: 6 hours
Latency and accuracy during a interoceptive stimulus task
Time frame: 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2020.
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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.
Martin P Paulus, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Methylphenidate in people with PTSD, run by University of California, San Diego 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 18 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 Feb 2020. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Changes in blood oxygenation level-dependent BOLD signal responses (time frame: 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Feb 2020.