Nitrous TRD Bipolar Depression
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo 50% nitrogen {inert}/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F) |
Drug: Placebo
50% nitrogen {inert}/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)
|
| Experimental: Nitrous Oxide 50% nitrous oxide/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F) |
Drug: Nitrous Oxide
50% nitrous oxide/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 Outcome Measures
- Profile of Mood States (POMS) Short Form to Assess for Rapid/Instantaneous Changes in Mood/Affect [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]
- Brief Psychiatric Rating Scale (BPRS) to Assess Psychotic or Hallucinogenic Behavior [up to 1 week]
- Scale for Suicidal Ideation (SSI) to Assesses for Emergence of Suicidal Thinking [up to 1 week]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
Sponsors and Collaborators
- Washington University School of Medicine
- Stanley Medical Research Institute
- PPD
Investigators
- Principal Investigator: Ben Palanca, MD, Washington University School of Medicine
Study Documents (Full-Text)
More Information
Publications
None provided.- 201509128
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | Nitrous Oxide |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Period Title: Overall Study | ||
| STARTED | 1 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo | Nitrous Oxide | Total |
|---|---|---|---|
| Arm/Group Description | 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) | 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) | Total of all reporting groups |
| Overall Participants | 1 | 0 | 1 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
NaN
|
0
0%
|
| Between 18 and 65 years |
0
0%
|
0
NaN
|
0
0%
|
| >=65 years |
1
100%
|
0
NaN
|
1
100%
|
| Age (years) [Mean (Full Range) ] | |||
| Mean (Full Range) [years] |
70
|
70
|
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
NaN
|
0
0%
|
| Male |
1
100%
|
0
NaN
|
1
100%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
1
100%
|
1
Infinity
|
|
Outcome Measures
| Title | Change in MADRS (Montgomery Asberg Depression Rating Scale) |
|---|---|
| Description | Change in depressive symptoms on MADRS scale between baseline and day 7 follow up |
| Time Frame | up to 1 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| Difficulty with recruitment caused study sponsor to end trial after designated award length; no analysis done |
| Arm/Group Title | Placebo | Nitrous Oxide |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Measure Participants | 0 | 0 |
| Title | Hamilton Depression Rating Scale-17 Item (Ham-D17) |
|---|---|
| Description | |
| Time Frame | up to1week |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Young Mania Rating Scale (YMRS) to Assess Emergence of Mania/Hypomania |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Profile of Mood States (POMS) Short Form to Assess for Rapid/Instantaneous Changes in Mood/Affect |
|---|---|
| Description | |
| Time Frame | up to 1 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Quick Inventory of Depressive Symptomatology- Self Report (QIDS -SR) Patient-rated Depression Measure |
|---|---|
| Description | |
| Time Frame | up to 1 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Clinician Administered Dissociative States Scale (CADSS) for Emergence of Disassociation |
|---|---|
| Description | |
| Time Frame | up to 1week |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Brief Psychiatric Rating Scale (BPRS) to Assess Psychotic or Hallucinogenic Behavior |
|---|---|
| Description | |
| Time Frame | up to 1 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Scale for Suicidal Ideation (SSI) to Assesses for Emergence of Suicidal Thinking |
|---|---|
| Description | |
| Time Frame | up to 1 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | 2 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | No participants enrolled in Nitrous Oxide arm | |||
| Arm/Group Title | Placebo | Nitrous Oxide | ||
| Arm/Group Description | 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) | 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) | ||
All Cause Mortality |
||||
| Placebo | Nitrous Oxide | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | 0/0 (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Nitrous Oxide | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | 0/1 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Nitrous Oxide | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | 0/0 (NaN) | ||
| General disorders | ||||
| Feeling more cold mostly in feet | 1/1 (100%) | 3 | 0/0 (NaN) | 0 |
| Nervous system disorders | ||||
| Headache | 1/1 (100%) | 1 | 0/0 (NaN) | 0 |
| Psychiatric disorders | ||||
| Worsened Anxiety | 1/1 (100%) | 1 | 0/0 (NaN) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Ben J Palanca, MD PhD MSC |
|---|---|
| Organization | Washington University |
| Phone | 314-286-0132 |
| palancab@wustl.edu |
- 201509128