Bipolar Depressive Disorder, Bipolar Disorder, Treatment- Resistant Bipolar Disorder
Conditions
Keywords
Bipolar Depressive Disorder, Treatment- Resistant Bipolar Disorder, Nitrous Oxide
Brief summary
Investigators will study approximately 64 patients with Treatment-Resistant Bipolar Depressive Disorder, defined as a failure of at least 1 antidepressants in the current depressive episode and 2 lifetime medication failures. The study will last approximately 6 to 8 weeks, involving randomization into one of two treatment groups receiving 3 one hour long inhalation treatments over a week.
Detailed description
Investigators will study approximately 64 patients with Treatment-Resistant Bipolar Depressive Disorder, defined as a failure of at least 1 antidepressants in the current depressive episode and 2 lifetime medication failures. The study will last approximately 6 to 8 weeks, involving randomization into one of two treatment groups receiving 3 one hour long inhalation treatments over a week. Post-treatment assessments follow each inhalation treatment and are conducted 1 week and 2 weeks following the final inhalation treatment. Patients are then randomized again into the Second Stage of the study, involving the same treatment and post-treatment schedule as the First Stage detailed above.
Interventions
DRUGNitrous Oxide
50% nitrous oxide/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)
DRUGPlacebo
50% nitrogen {inert}/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)
Sponsors
Stanley Medical Research Institute
PPD Development, LP
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adults 18-65 years of age * Treatment-resistant bipolar depressive disorder without psychosis and a MADRS baseline score of \>20. All patients must have history of being on a serum-verified (at time of entry into study) mood stabilizer \[lithium at 0.5-1.2mEq/L; or valproic acid, 50-125mcg/ml\] for 4 weeks prior to entry into the study and remain on this mood stabilizer during the course of the trial. Further, subjects will have failed two adequate dose/duration antidepressant courses in their lifetime, including one in the current depressive episode (verified by Antidepressant Treatment History Form). * Good command of the English language
Exclusion criteria
* Schizophrenia * Schizoaffective disorder * Obsessive-compulsive disorder or panic disorder * Active or recent substance abuse or dependence (in remission at least 1 year prior to the study; exception = nicotine use disorders) * A diagnosis of personality disorder that may interfere with the patient's ability to improve on nitrous oxide as determined by study investigator * Acute medical illness that may pose subject at risk during nitrous oxide administration (neurological disorders or medical disorders including dementia, stroke, encephalopathy, Parkinson's Disease, brain tumors, multiple sclerosis, seizure disorder, severe cardiac disease, any disease known to affect drug metabolism and excretion, i.e. renal or liver disease) per P.I. discretion * Active suicidal intention (inability to contract for safety) * Active psychotic symptoms * Patients with significant pulmonary disease and/or requiring supplemental oxygen * Contraindication against the use of nitrous oxide: pneumothorax; bowel obstruction; middle ear occlusion; elevated intracranial pressure; chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12; pregnant patients; breastfeeding women; previous administration of NMDA-receptor antagonists (e.g., ketamine); current electro-convulsive therapy treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in MADRS (Montgomery Asberg Depression Rating Scale) | up to 1 week | Change in depressive symptoms on MADRS scale between baseline and day 7 follow up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale-17 Item (Ham-D17) | up to1week | — |
| Young Mania Rating Scale (YMRS) to Assess Emergence of Mania/Hypomania | up to 1 week | Young Mania Rating Scale (YMRS) to assess emergence of mania/hypomania (patients with YMRS scores \> 12 will be removed from the trial and recommended for follow up treatment per Psychiatry P.I., i.e., nitrous oxide treatments discontinued) |
Other
| Measure | Time frame |
|---|---|
| Brief Psychiatric Rating Scale (BPRS) to Assess Psychotic or Hallucinogenic Behavior | up to 1 week |
| Profile of Mood States (POMS) Short Form to Assess for Rapid/Instantaneous Changes in Mood/Affect | up to 1 week |
| Scale for Suicidal Ideation (SSI) to Assesses for Emergence of Suicidal Thinking | up to 1 week |
| Quick Inventory of Depressive Symptomatology- Self Report (QIDS -SR) Patient-rated Depression Measure | up to 1 week |
| Clinician Administered Dissociative States Scale (CADSS) for Emergence of Disassociation | up to 1week |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 50% nitrogen {inert}/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)
Placebo: 50% nitrogen {inert}/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F) | 1 |
| Nitrous Oxide 50% nitrous oxide/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)
Nitrous Oxide: 50% nitrous oxide/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F) | 0 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Nitrous Oxide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 70 years | — | 70 years |
| Region of Enrollment United States | 1 participants | — | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Change in MADRS (Montgomery Asberg Depression Rating Scale)
Change in depressive symptoms on MADRS scale between baseline and day 7 follow up
Time frame: up to 1 week
Population: Difficulty with recruitment caused study sponsor to end trial after designated award length; no analysis done
Secondary
Hamilton Depression Rating Scale-17 Item (Ham-D17)
Time frame: up to1week
Secondary
Young Mania Rating Scale (YMRS) to Assess Emergence of Mania/Hypomania
Young Mania Rating Scale (YMRS) to assess emergence of mania/hypomania (patients with YMRS scores \> 12 will be removed from the trial and recommended for follow up treatment per Psychiatry P.I., i.e., nitrous oxide treatments discontinued)
Time frame: up to 1 week
Other Pre-specified
Brief Psychiatric Rating Scale (BPRS) to Assess Psychotic or Hallucinogenic Behavior
Time frame: up to 1 week
Other Pre-specified
Clinician Administered Dissociative States Scale (CADSS) for Emergence of Disassociation
Time frame: up to 1week
Other Pre-specified
Profile of Mood States (POMS) Short Form to Assess for Rapid/Instantaneous Changes in Mood/Affect
Time frame: up to 1 week
Other Pre-specified
Quick Inventory of Depressive Symptomatology- Self Report (QIDS -SR) Patient-rated Depression Measure
Time frame: up to 1 week
Other Pre-specified
Scale for Suicidal Ideation (SSI) to Assesses for Emergence of Suicidal Thinking
Time frame: up to 1 week