Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression.
<h4>Background</h4>Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding....
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297330&type=printable |
| _version_ | 1797326174461886464 |
|---|---|
| author | Karim S Ladha Jiwon Lee Gabriella F Mattina Janneth Pazmino-Canizares Duminda N Wijeysundera Fatemeh Gholamali Nezhad Kaylyssa Philip Vanessa K Tassone Fathima Adamsahib Venkat Bhat SMILE Study Investigators |
| author_facet | Karim S Ladha Jiwon Lee Gabriella F Mattina Janneth Pazmino-Canizares Duminda N Wijeysundera Fatemeh Gholamali Nezhad Kaylyssa Philip Vanessa K Tassone Fathima Adamsahib Venkat Bhat SMILE Study Investigators |
| author_sort | Karim S Ladha |
| collection | DOAJ |
| description | <h4>Background</h4>Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam.<h4>Methods</h4>In this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score <10), response (defined as ≥ 50% reduction in MADRS score), and adverse side effects.<h4>Discussion</h4>This pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression.<h4>Trial registration</h4>ClinicalTrials.gov NCT04957368. Registered on July 12, 2021. |
| first_indexed | 2024-03-08T06:20:41Z |
| format | Article |
| id | doaj.art-b9ea1238f7124ba5bf1e2f22443a6743 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-08T06:20:41Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b9ea1238f7124ba5bf1e2f22443a67432024-02-04T05:31:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01191e029733010.1371/journal.pone.0297330Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression.Karim S LadhaJiwon LeeGabriella F MattinaJanneth Pazmino-CanizaresDuminda N WijeysunderaFatemeh Gholamali NezhadKaylyssa PhilipVanessa K TassoneFathima AdamsahibVenkat BhatSMILE Study Investigators<h4>Background</h4>Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam.<h4>Methods</h4>In this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score <10), response (defined as ≥ 50% reduction in MADRS score), and adverse side effects.<h4>Discussion</h4>This pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression.<h4>Trial registration</h4>ClinicalTrials.gov NCT04957368. Registered on July 12, 2021.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297330&type=printable |
| spellingShingle | Karim S Ladha Jiwon Lee Gabriella F Mattina Janneth Pazmino-Canizares Duminda N Wijeysundera Fatemeh Gholamali Nezhad Kaylyssa Philip Vanessa K Tassone Fathima Adamsahib Venkat Bhat SMILE Study Investigators Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. PLoS ONE |
| title | Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. |
| title_full | Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. |
| title_fullStr | Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. |
| title_full_unstemmed | Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. |
| title_short | Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. |
| title_sort | sustained mood improvement with laughing gas exposure smile study protocol for a randomized placebo controlled pilot trial of nitrous oxide for treatment resistant depression |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297330&type=printable |
| work_keys_str_mv | AT karimsladha sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT jiwonlee sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT gabriellafmattina sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT jannethpazminocanizares sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT dumindanwijeysundera sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT fatemehgholamalinezhad sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT kaylyssaphilip sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT vanessaktassone sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT fathimaadamsahib sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT venkatbhat sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression AT smilestudyinvestigators sustainedmoodimprovementwithlaughinggasexposuresmilestudyprotocolforarandomizedplacebocontrolledpilottrialofnitrousoxidefortreatmentresistantdepression |