Obsessive-Compulsive Disorder
Conditions
Keywords
D-amphetamine, dextro-amphetamine, stimulant drug
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.
Interventions
DRUGdextro-amphetamine
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.
DRUGSham Comparison
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
Sponsors
Obsessive Compulsive Foundation
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Clinical Global Impressions Scale - Improvement (CGI-I) Score of 1 or 2 | At end of week 5, except 1 d-amphetamine subject rated at end of week 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). |
| Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) Score | At end of week 5, except 1 d-amphetamine subject rated at end of week 2 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D-amphetamine Dextro-amphetamine: 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.
Caffeine dosage form: 200 mg capsules in Bottle A, 100 mg capsules in Bottle B. Dosage: One capsule from Bottle A and one capsule from bottle B each morning. Frequency: once daily. Duration: 5 weeks. | 12 |
| Caffeine Pills 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. Frequency: once daily. Duration: 5 weeks | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 4-week Study Continuation Phase | Lack of Efficacy | 1 | 0 |
| First Study Week | Lack of Efficacy | 6 | 5 |
Baseline characteristics
| Characteristic | D-amphetamine | Caffeine Pills | Total |
|---|---|---|---|
| Age, Continuous Baseline Age | 42.3 years STANDARD_DEVIATION 12.8 | 37.8 years STANDARD_DEVIATION 13.7 | 40.05 years STANDARD_DEVIATION 13.25 |
| Atypical antipsychotic drug augmentation trials | 2.4 trials | 2.5 trials | 2.5 trials |
| Prior Selective Serotonin Reuptake or Serotonin Norepinephrine Reuptake Inhibitor trials | 3.0 trials | 3.7 trials | 3.4 trials |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 4 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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).
Time frame: At end of week 5, except 1 d-amphetamine subject rated at end of week 2
Population: Subjects who met the study continuation phase entry criterion of \>20% decrease in Y-BOCS score after 1 week of double-blind study medication, and entered this 4-week double-blind continuation phase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| D-amphetamine | Number of Subjects With Clinical Global Impressions Scale - Improvement (CGI-I) Score of 1 or 2 | 6 participants |
| Caffeine Pills | Number of Subjects With Clinical Global Impressions Scale - Improvement (CGI-I) Score of 1 or 2 | 7 participants |
Primary
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.
Time frame: At end of week 5, except 1 d-amphetamine subject rated at end of week 2
Population: Subjects who entered the 4-week double-blind study continuation phase, including a last observation carried forward for the one d-amphetamine subject who dropped out of this phase at the end of study week 2 (end of the first week of the continuation phase) for lack of efficacy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-amphetamine | Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) Score | 13.3 units on a scale | Standard Deviation 6.9 |
| Caffeine Pills | Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) Score | 13.0 units on a scale | Standard Deviation 8.4 |