Effects of Methylphenidate (Ritalin®) on the Neural Basis of Anxiety



Status:Recruiting
Conditions:Psychiatric
Therapuetic Areas:Psychiatry / Psychology
Healthy:No
Age Range:18 - 40
Updated:5/5/2014
Start Date:March 2014
Contact:Martin P Paulus, MD
Email:RitalinStudy@ucsd.edu
Phone:858 534 9444

Use our guide to learn which trials are right for you!

Effects of Methylphenidate (Ritalin®) on the Neural Basis of Anxiety: a Placebo-controlled fMRI Study in Healthy Male Subjects

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.


Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

- 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.
We found this trial at
1
site
San Diego, California 92037
?
mi
from
San Diego, CA
Click here to add this to my saved trials