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Trial record 9 of 439 for:    Methylphenidate

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

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ClinicalTrials.gov Identifier: NCT02021214
Recruitment Status : Completed
First Posted : December 27, 2013
Last Update Posted : December 3, 2014
Sponsor:
Information provided by (Responsible Party):
Martin Paulus, University of California, San Diego

Brief 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. 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.

Condition or disease Intervention/treatment Phase
PTSD Drug: Methylphenidate Drug: Placebo Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Methylphenidate (Ritalin®) on the Neural Basis of Anxiety: a Placebo-controlled fMRI Study in Healthy Male Subjects
Study Start Date : March 2014
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Experimental: Methylphenidate/Placebo
40 mg Methylphenidate, per os, single dose or Placebo
Drug: Methylphenidate
Other Name: Ritalin

Drug: Placebo



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Changes in BOLD signal responses [ Time Frame: 6 hours ]
    Methylphenidate induced changes in BOLD signal responses in regions implicated in emotional processing while anticipating a positive interoceptive stimulus compared to placebo.

  2. Changes in skin conductance response [ Time Frame: 6 hours ]
    Changes compared to placebo in skin conductance respo during a fear extinction task

  3. Latency and accuracy during a interoceptive stimulus task [ Time Frame: 2 hours ]
    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



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02021214


Locations
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United States, California
UCSD Psychiatry Clinical Research
San Diego, California, United States, 92037
Sponsors and Collaborators
University of California, San Diego
Investigators
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Principal Investigator: Martin P Paulus, MD University of California, San Diego

Additional Information:
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Responsible Party: Martin Paulus, Adjunct Professor of Psychiatry, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02021214     History of Changes
Other Study ID Numbers: 131297
First Posted: December 27, 2013    Key Record Dates
Last Update Posted: December 3, 2014
Last Verified: December 2014
Keywords provided by Martin Paulus, University of California, San Diego:
Methylphenidate
Fear extinction
fMRI
mPFC
Additional relevant MeSH terms:
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Methylphenidate
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents