Proceed: Pragmatic Trial of Obsessive-compulsive Disorder
Study Details
Study Description
Brief Summary
This study includes a sequenced clinical trial in order to assess the efficacy of several switching or augment strategies when initial treatment is ineffective，and to provide strong evidence for clinical practice and international guidelines for Obsessive-Compulsive Disorder treatments.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Selective Serotonin Reuptake Inhibitors(SSRIs) are the first line pharmacotherapy for Obsessive-Compulsive Disorder (OCD) according to APA（American Psychological Association）guideline. Nevertheless, a large proportion (40% or more) of patients response only partially or not at all to treatment with a SSRI. On the basis of the existing sparse literature, several pharmacotherapy options for OCD patients who do not respond, or who respond but do not remit, have been outlined in current treatment guidelines. These include
- treatment with higher than usual doses of an SSRI, 2) switch to a different SSRI, 3) switch to a different class of medication, 4) augmentation with a dopamine blocker, and 5) augmentation with a glutamatergic agent. There is a need for additional data, particularly real-world data, on how best to choose between these options.
This proposed Randomized Controlled Trial (RCT) study is a multi-center clinical study with a total of 13 centers that specialize in OCD patients. A randomized block design will be used in this study and all eligible participants accepted into this study will undergo an initial course of pharmacotherapy (phase I), and non-remmitters will be randomly allocated to five treatment arms (phase II). In phase I all participants will be treated with sertraline for 12 weeks.In phase II,The 5 arms will comprise 1) treatment with higher than usual doses of sertraline, 2) switch to fluvoxamine, 3) switch to venlafaxine, 4) augmentation with memantine, and 5) augmentation with aripiprazole. Clinicians and patients will know which treatment arm is being employed, but raters will be kept blind to treatment group.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: serotonin treatment In experimental phase I, all recruited subjects provide written informed consent before any related procedures. Participants will receive sertraline, initially at 50mg/d, with a weekly 50mg/d further increase, to the maximum recommended dosage (200mg/d) or to the maximum tolerated dosage (less than 200mg/d). Patients will be on their maximum dose by week 4, so allowing an assessment of response at 12 weeks |
Drug: Sertraline 200 milligram(mg)
All included participants will receive sertraline, initially at 50mg/d, with a weekly 50mg/d further increase, to the maximum recommended dosage (200mg/d) or to the maximum tolerated dosage (less than 200mg/d). Patients will be on their maximum dose by week 4, so allowing an assessment of response at 12 weeks
|
| Active Comparator: sequenced treatment alternatives If participants in In Experimental phase I do not achieve remission, they will be will be randomly assigned to the second-step treatment (Experimental phase II). The second-step therapy will consist of five treatment options including higher-than-usual-maximal dosage of sertraline, switching to fluvoxamine, switching to venlafaxine, augmentation with memantine, and augmentation with aripiprazole. |
Drug: Sertraline 300 milligram(mg)
In experimental phase II, the patients in this group will remain on sertraline (higher dosage): where sertraline 200mg has been tolerated, dosage will be increased by 50mg fortnightly to a maximal dose of 300mg/d or to the maximum tolerable dose (less than 300mg/d).
Drug: Fluvoxamine
Fluvoxamine will be initiated at a dose of 50mg/d, increasing quickly to a maximal dose of 300mg/d or the maximum tolerated dose by week 4.
Drug: Venlafaxine
venlafaxine will be initiated at 75mg/d, increasingly weekly by 75mg/day, to a maximal dose of 300 mg/d or the maximum tolerated dose.
Drug: Augment with Memantine
Sertraline will be augmented with memantine initially at 5mg/d, and increasing by 5mg/d weekly to a maximal dose of 20mg/d (10mg twice daily) or the maximum tolerated dose
Drug: Augment with Aripiprazole
Sertraline will be augmented with aripiprazole, initially at 5mg/d, and increasing by 5mg/d weekly to a maximal dose of 20mg/d or the maximum tolerated dose
|
Outcome Measures
Primary Outcome Measures
- Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [from baseline to 12 weeks, and 12 weeks to month 6.]
Y-BOCS is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms), with separate subtotals for severity of obsessions and compulsions.Patients will be assessed at baseline, week 2, week 4, week 8, week 12, week 16, week 20, month 6.
Secondary Outcome Measures
- The Clinical Global Impression (CGI) [from 2 weeks to 12 weeks, and 12 weeks to month 6.]
The Clinical Global Impression (CGI; National Institute of Mental Health) is a clinician-rated scale to assess treatment response in patients with mental disorders. The scale contains three items: Severity of Illness; Global Improvement; Efficacy Index. It requires the clinician to rate how much the patient's illness has improved or worsened relative to a baseline measurement. Patients will be assessed at week 2, week 4, week 8, week 12, week 16, week 20, month 6.
- Beck Anxiety Inventory (BAI) [from baseline to 12 weeks, and 12 weeks to month 6.]
BAI is a 21-item inventory which identifies anxiety symptoms and quantifies their intensity. Patients will be assessed at baseline, week 2, week 4, week 8, week 12, week 16, week 20, month 6.
- Beck Depression Inventory-Ⅱ(BDI-Ⅱ) [from baseline to 12 weeks, and 12 weeks to month 6.]
BDI-Ⅱ is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression.Patients will be assessed at baseline, week 2, week 4, week 8, week 12, week 16, week 20, month 6.
- Obsessive-Compulsive Inventory-Revised(OCI-R) [from baseline to 12 weeks, and 12 weeks to month 6.]
OCI-R is the measure of election for the assessment of obsessive-compulsive behaviors, given its validity and the short time that its administration requires. Patients will be assessed at baseline, week 2, week 4, week 8, week 12, week 16, week 20, month 6.
- Sheehan Disability Scale(SDS) [from baseline to 12 weeks, and 12 weeks to month 6.]
The Sheehan Disability Scale is a three item self-rated scale of impairment. The items address the impact of symptomatology on three areas of functioning: work, social and family. The SDS use an 11-point (0-10) scale with the number '0' signifying no impairment and the number '10' signifying the highest (' extremely') impairment. Patients will be assessed at baseline, week 2, week 4, week 8, week 12, week 16, week 20, month 6.
- Treatment Emergent Symptom Scale (TESS) [from 2 weeks to 12 weeks , and 12 weeks to month 6.]
The Treatment Emergent Symptom Scale (TESS) is used to record side effects. The side effects are assessed on a five-point scale ranging from 0 ("no side effects") to 4 ("severe side effects"). Patients will be assessed at week 2, week 4, week 8, week 12, week 16, week 20, month 6.
- Tolerability scale [from 2 weeks to 12 weeks , and 12 weeks to month 6.]
The tolerability of treatment will be defined as side effect discontinuation in this study. as defined by the proportion of patients who discontinued treatment due to adverse events during the study.Patients will be assessed at week 2, week 4, week 8, week 12, week 16, week 20, month 6.
Other Outcome Measures
- Complete Blood Count [baseline]
for safety considerations
Eligibility Criteria
Criteria
Inclusion criteria:They
-
meet DSM-5 diagnostic criteria for OCD as the primary diagnosis ;
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are in the age range from 18 to 65 years;
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have a score of at least 20 on Yale-Brown Obsessive-Compulsive Scale (Y-BOCS);
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have never received medication for OCD, and have not received any form of psychotherapy for OCD in the past 1 month;
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have provided written informed consent.
exclusion criteria: They
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have met the DSM-5 diagnostic criteria for Schizophrenia Spectrum and Other Psychotic Disorders, or the Bipolar and Related Disorders;
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have a moderate or higher risk of suicide (⩾9 on the Suicide Module in the Mini-International Neuropsychiatric Interview (MINI));
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have substance use that is sufficiently severe to possibly impact negatively on treatment adherence in the past 1 year;
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have severe depression with Beck Depression Inventory-II (BDI-II) score of ≥29;
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have comorbid psychiatric or medical disorders that may impact negatively on adherence to or on the efficacy of medication (eg borderline personality disorder, CNS disorders)；
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are pregnant or lactating females.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shanghai Mental Health Center | Shanghai | Shanghai | China | 200030 |
Sponsors and Collaborators
- Shanghai Mental Health Center
- The first specialized hospital of harbin
- Guizhou Provincial People's Hospital
- First Affiliated Hospital of Jinan University
- West China Hospital
- Suzhou Psychiatric Hospital
- Nanjing Medical University
- Wuhan Mental Health Centre
- Seventh People's Hospital of Hangzhou
- The First Affiliated Hospital of Kunming Medical College
- General Hospital of Ningxia Medical University
- The First Affiliated Hospital of Nanchang University
- The Second Affiliated Hospital of Xinxiang Medical University
Investigators
- Principal Investigator: Zhen Wang, PhD,MD, Shanghai Mental Health Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CRC2018ZD03