Dextro-Amphetamine Versus Caffeine in Treatment-resistant OCD

Study Overview
=================
Brief Summary
-----------------
The study hypothesis is that dextro-amphetamine (d-amphetamine) will be safe and effective when used to augment treatment for Obsessive-Compulsive Disorder (OCD), and that tolerance (loss of therapeutic effect) to the medication will not develop over a period of several weeks.

Detailed Description
-----------------
The study will investigate whether dextro-amphetamine (d-amphetamine) is safe and effective compared to caffeine as an active placebo when used to augment treatment for Obsessive-Compulsive Disorder (OCD), and whether tolerance (loss of therapeutic effect) to the medication will develop over a period of several weeks D-amphetamine is approved by the U.S. Food and Drug Administration to treat Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents. Because of the effects that d-amphetamine has on the brain, Dr. Koran believes it may be helpful in treating OCD. A positive finding in this study may stimulate research aimed at improving OCD treatment and understanding of the neurochemistry involved. This research study will enroll 24 people who are taking medication for their OCD but are not receiving sufficient benefit. The research will be performed only at Stanford University.

Official Title
-----------------
Double-blind Trial of Acute and Intermediate-term Dextro-amphetamine Versus Caffeine Augmentation in Treatment Resistant Obsessive Compulsive Disorder (OCD)

Conditions
-----------------
Obsessive-Compulsive Disorder

Intervention / Treatment
-----------------
* Drug: dextro-amphetamine
* Drug: Sham Comparison


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: outpatient age 18 through 55 inclusive meets DSM-IV criteria for obsessive-compulsive disorder (OCD) with Yale-Brown Obsessive-Compulsive Scale (YBOCS) score greater than or equal to 20 provides written informed consent has taken for at least 12 weeks at least the dose shown of a selective serotonin reuptake inhibitor (SSRI) [citalopram, escitalopram, or fluoxetine 20 mg/d; paroxetine 40 mg/d; sertraline 50 mg/d]; or venlafaxine 225 mg/d; or duloxetine 60 mg/d. if taking buspar, gabapentin, an atypical antipsychotic, or a benzodiazepine, dose has been stable for 4 weeks has negative urine drug and pregnancy tests is practicing reliable birth control method has blood pressure readings at screening visit that are less than 140 mm Hg systolic and 90 mm Hg diastolic, weight is greater than 100 lbs at screen Exclusion criteria: requires psychotropic medications other than an Serotonin Reuptake Inhibitor (SRI), a benzodiazepine, buspirone, an atypical antipsychotic, and/or gabapentin is taking clomipramine is taking fluvoxamine is taking medication that inhibits hepatic enzyme CYP1A2 is taking a monoamine oxidase inhibitor has co-morbid tics or Tourette's disorder has hoarding as the primary or only OCD symptom has a history of panic disorder has a history of glaucoma has a history of seizures has a history of schizophrenia or psychotic disorder, or schizotypal personality disorder has depression with current suicide risk has mental retardation, pervasive developmental disorder, or cognitive disorder has a factitious disorder has current or past cyclothymic disorder or bipolar disorder has a dissociative disorder has personality disorder sufficient to interfere with study participation has organic mental disorder or dementia has current or past substance abuse / dependence (excluding nicotine) has current or past anorexia or bulimia has serious or unstable medical disorder, including hypertension or cardiac disease has history of myocardial infarction or cardiac arrhythmia has history of or has current diagnosis of hypertension is pregnant or breast-feeding is receiving psychotherapy for OCD is intending to receive psychotherapy for OCD during the study has had a previous trial of d-amphetamine of at least 30 days duration is unable to speak, read, or understand English is not likely to follow study procedures is not suitable for study in the investigator's opinion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: d-amphetamine<br>dextro-amphetamine capsules, 15 mg per capsule, in Bottles A and B, dose: one from Bottle A each morning and 1 from Bottle B each morning | Drug: dextro-amphetamine<br>* dextro-amphetamine dosage form: 15 mg capsules, in Bottles A and B. Dosage: One capsule from Bottle A and one capsule from bottle B each morning. Frequency: once daily. Duration: 5 weeks.<br>* Other names: Dexedrine;|
| Sham Comparator: Sham comparison<br>caffeine in capsules identical to those containing d-amphetamine, with 200 mg of caffeine in Bottle A capsules, and 100 mg of caffeine in Bottle B capsules, dose was 1 capsule from Bottle A and 1 capsule from Bottle B each morning | Drug: Sham Comparison<br>* caffeine dosage form: capsules identical to those in dextro-amphetamine arm, but containing 200 mg caffeine in Bottle A and 100 mg caffeine in Bottle B. Frequency: once daily. Duration: 5 weeks<br>* Other names: Caffeine, 300 mg/day;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Clinical Global Impressions Scale - Improvement (CGI-I) Score of 1 or 2 | Clinical Global Impressions Scale Improvement Score = 1 (very much improved), or 2 (much improved). Additional possible scale scores are 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). | At end of week 5, except 1 d-amphetamine subject rated at end of week 2 | 
| Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) Score | Yale-Brown Obsessive-Compulsive Scale score by blinded investigator in direct interview. The scale score is the sum of ten items (5 for obsessions and 5 for compulsions: time occupied, degree of interference with functioning, degree of distress, effort to resist the symptom, success in resisting), each rated from 0 to 4, with higher scores indicating more severe OCD. Maximum score is 40. Scores of 14 and below are often described as subclinical, though patients with these scores may still exhibit troubling symptoms and mild to moderate distress. A total score of 8 or less is often termed remission. A decrease in total score from baseline to endpoint of either 25% or 35% is often used as a responder criterion in clinical trials. | At end of week 5, except 1 d-amphetamine subject rated at end of week 2 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
D-amphetamine, dextro-amphetamine, stimulant drug