Depressive Disorder, Treatment-ResistantNCT05008939
Sevoflurane for Treatment-Resistant Depression
A study testing Sevoflurane in people with Depressive Disorder, Treatment-Resistant and Depressive Disorder, Major, run by Shanghai First Maternity and Infant Hospital at 1 site in China.
Trial summary
This study intends to carry out a prospective, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subanesthetic sevoflurane for treatment-resistant depression. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major
- What is being tested?
- Sevoflurane
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- Aug 2021to Mar 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age 18-65 years
- meeting DSM-V criteria for major depressive disorder
- a pretreatment score ≥17 on HDRS-17
- meeting criteria for TRD, defined as having had at least two adequate dose-duration antidepressant medication failures in the current depressive episode.
- current treatment drugs were stably used for at least 4 weeks
Who cannot join
- MDD with psychosis, e.g., bipolar disorder, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, panic disorder, et al
- Drug, tobacco or alcohol abuse
- active suicidal intention
- previous administration of NMDA receptor antagonists (e.g., ketamine)
- previous (<6 weeks prior) or ongoing treatment with electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS)
- pregnancy or breastfeeding
- morbidly obese, BMI>35kg/m2
- other diseases that could interfere with the results
Trial locations and contacts
1 site in 1 country.
China1 site
Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine
Shanghai, Shanghai Municipality, 02148
Fuyi Shen, MD, 86-13524123072, shenfuyi315@sina.com
Zhiqiang Liu, MD, 86-13816877756, drliuzhiqiang@163.com
About this study
Official title: Subanesthetic Sevoflurane for Treatment-Resistant Depression: A Proof-of-Concept Trial
This study intends to carry out a prospective, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subanesthetic sevoflurane for treatment-resistant depression.
- Being tested
- Sevoflurane, Placebo
- Keywords
- treatment-resistant depression (TRD), major depressive disorder (MDD), sevoflurane
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SevofluraneDrug
Also called Treatment
Patients receive 1% sevoflurane and 30% oxygen for 1 hour.
PlaceboDrug
Also called Control
Patients received 30% oxygen for 1 hour.
| Study group | Role | What they receive |
|---|---|---|
| sevoflurane | Experimental | Those with 1-hour inhalation of 1% sevoflurane/30% oxygen Receives: Drug: Sevoflurane; Drug: Placebo |
| placebo | Placebo comparator | Those with 1-hour inhalation of 30% oxygen Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rates of treatment responses in 17-item Hamilton Depression Rating Scale (HDRS-17)
≥50% HDRS-17 reduction in depressive symptoms
Measured: 24 hours after the end of treatment
Secondary outcomes (11)
Rates of treatment responses in HDRS-17
≥50% HDRS-17 reduction in depressive symptoms
Measured: 2 hours, 7 days,14 days and 28 days after the end of treatment
Rates of remissions in HDRS-17
HDRS-17 ≤7 points
Measured: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Rates of treatment responses in Montgomery-Åsberg Depression Rating Scale (MADRS)
≥50% MADRS reduction in the baseline score
Measured: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Rates of remissions in MADRS
MADRS <10
Measured: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of depression with self-rating scale
The changes of score in Patient Health Questionnaire-9 (PHQ-9)
Measured: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of anxiety by psychiatrist
The changes of score in Hamilton Anxiety Rating Scale (HAMA)
Measured: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of anxiety with self-rating scale
The changes of score in Generalized Anxiety Disorder Screener (GAD-7)
Measured: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of improvement by psychiatrist
The changes of score in Clinical Global Impression (CGI)
Measured: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of improvement with self-rating scale
The changes of score in Patient Global Impressions of Improvement (PGI-I)
Measured: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of side effects with self-rating scale
Including Patient Rated Inventory of Side Effects (PRISE)
Measured: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Side effects of sevoflurane
Including nausea, vomiting, headache, dizzy, hypotension, hypoxemia, carbon dioxide accumulation, et al
Measured: up to 2 hours after the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2021
- Study startAug 2021 (estimated)
- Primary completionMar 2022 (estimated)
- Study completionMar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Depressive Disorder, Treatment-ResistantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai First Maternity and Infant Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University
- Responsible party
- Sponsor
- Investigators
- Zhiqiang Liu, MD, Study chair, Department of Anesthesiaology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05008939
- Sponsor's protocol ID
- ShanghaiFMIH2021 Zhiqiang Liu
- Status last verified
- Aug 2021
- First submitted
- 25 Jul 2021
- Last updated
- 17 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gaynes BN, Warden D, Trivedi MH, Wisniewski SR, Fava M, Rush AJ. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009 Nov;60(11):1439-45. doi: 10.1176/ps.2009.60.11.1439.
PubMed 19880458Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006 Jan;163(1):28-40. doi: 10.1176/appi.ajp.163.1.28.
PubMed 16390886Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013. Psychiatr Serv. 2014 Aug 1;65(8):977-87. doi: 10.1176/appi.ps.201300059.
PubMed 24789696Papakostas GI, Petersen TJ, Farabaugh AH, Murakami JL, Pava JA, Alpert JE, Fava M, Nierenberg AA. Psychiatric comorbidity as a predictor of clinical response to nortriptyline in treatment-resistant major depressive disorder. J Clin Psychiatry. 2003 Nov;64(11):1357-61. doi: 10.4088/jcp.v64n1112.
PubMed 14658951Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS; Scientific Advisory Board and the Executive Committee of the Grand Challenges on Global Mental Health; Anderson W, Dhansay MA, Phillips A, Shurin S, Walport M, Ewart W, Savill SJ, Bordin IA, Costello EJ, Durkin M, Fairburn C, Glass RI, Hall W, Huang Y, Hyman SE, Jamison K, Kaaya S, Kapur S, Kleinman A, Ogunniyi A, Otero-Ojeda A, Poo MM, Ravindranath V, Sahakian BJ, Saxena S, Singer PA, Stein DJ. Grand challenges in global mental health. Nature. 2011 Jul 6;475(7354):27-30. doi: 10.1038/475027a. No abstract available.
PubMed 21734685Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry. 2007 Jan;52(1):46-54. doi: 10.1177/070674370705200108.
PubMed 17444078Sanacora G, Schatzberg AF. Ketamine: promising path or false prophecy in the development of novel therapeutics for mood disorders? Neuropsychopharmacology. 2015 Mar 13;40(5):1307. doi: 10.1038/npp.2014.338. No abstract available.
PubMed 25767082Chen C, Ji M, Xu Q, Zhang Y, Sun Q, Liu J, Zhu S, Li W. Sevoflurane attenuates stress-enhanced fear learning by regulating hippocampal BDNF expression and Akt/GSK-3beta signaling pathway in a rat model of post-traumatic stress disorder. J Anesth. 2015 Aug;29(4):600-8. doi: 10.1007/s00540-014-1964-x. Epub 2014 Dec 23.
PubMed 25533726Zhang H, Li L, Sun Y, Zhang X, Zhang Y, Xu S, Zhao P, Liu T. Sevoflurane prevents stroke-induced depressive and anxiety behaviors by promoting cannabinoid receptor subtype I-dependent interaction between beta-arrestin 2 and extracellular signal-regulated kinases 1/2 in the rat hippocampus. J Neurochem. 2016 May;137(4):618-29. doi: 10.1111/jnc.13613. Epub 2016 Mar 31.
PubMed 26991409Luo C, Zhang YL, Luo W, Zhou FH, Li CQ, Xu JM, Dai RP. Differential effects of general anesthetics on anxiety-like behavior in formalin-induced pain: involvement of ERK activation in the anterior cingulate cortex. Psychopharmacology (Berl). 2015 Dec;232(24):4433-44. doi: 10.1007/s00213-015-4071-2. Epub 2015 Sep 24.
PubMed 26400403Guo Z, Zhao F, Wang Y, Wang Y, Geng M, Zhang Y, Ma Q, Xu X. Sevoflurane Exerts an Anti-depressive Action by Blocking the HMGB1/TLR4 Pathway in Unpredictable Chronic Mild Stress Rats. J Mol Neurosci. 2019 Dec;69(4):546-556. doi: 10.1007/s12031-019-01380-2. Epub 2019 Jul 31.
PubMed 31368063
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subanesthetic Sevoflurane for Treatment-Resistant Depression: A Proof-of-Concept Trial
- ClinicalTrials.gov ID
- NCT05008939
- Acronym / sponsor ID
- ShanghaiFMIH2021 Zhiqiang Liu
- Keywords
- treatment-resistant depression (TRD), major depressive disorder (MDD), sevoflurane
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Shanghai First Maternity and Infant HospitalUniversity, hospital or other
- Collaborators
- Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University
- Study start
- Aug 2021 (estimated)
- Primary completion
- Mar 2022 (estimated)
- Study completion
- Mar 2022 (estimated)
- First posted
- 17 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study intends to carry out a prospective, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subanesthetic sevoflurane for treatment-resistant depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sevoflurane | Experimental | Drug: Sevoflurane, Drug: PlaceboThose with 1-hour inhalation of 1% sevoflurane/30% oxygen |
| placebo | Placebo comparator | Drug: PlaceboThose with 1-hour inhalation of 30% oxygen |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- age 18-65 years
- meeting DSM-V criteria for major depressive disorder
- a pretreatment score ≥17 on HDRS-17
- meeting criteria for TRD, defined as having had at least two adequate dose-duration antidepressant medication failures in the current depressive episode.
- current treatment drugs were stably used for at least 4 weeks
Key exclusion criteria (8 listed)
- MDD with psychosis, e.g., bipolar disorder, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, panic disorder, et al
- Drug, tobacco or alcohol abuse
- active suicidal intention
- previous administration of NMDA receptor antagonists (e.g., ketamine)
- previous (<6 weeks prior) or ongoing treatment with electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SevofluraneAlso: TreatmentPatients receive 1% sevoflurane and 30% oxygen for 1 hour. | Drug | sevoflurane |
| PlaceboAlso: ControlPatients received 30% oxygen for 1 hour. | Drug | placebo, sevoflurane |
Primary outcome
Rates of treatment responses in 17-item Hamilton Depression Rating Scale (HDRS-17)
Time frame: 24 hours after the end of treatment
≥50% HDRS-17 reduction in depressive symptoms
11 secondary outcomes
Rates of treatment responses in HDRS-17
Time frame: 2 hours, 7 days,14 days and 28 days after the end of treatment
Rates of remissions in HDRS-17
Time frame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Rates of treatment responses in Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Rates of remissions in MADRS
Time frame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of depression with self-rating scale
Time frame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of anxiety by psychiatrist
Time frame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of anxiety with self-rating scale
Time frame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of improvement by psychiatrist
Time frame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of improvement with self-rating scale
Time frame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
The assessment of side effects with self-rating scale
Time frame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Side effects of sevoflurane
Time frame: up to 2 hours after the end of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2021.
- Background: PubMed 19880458Gaynes BN, Warden D, Trivedi MH, Wisniewski SR, Fava M, Rush AJ. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009 Nov;60(11):1439-45. doi: 10.1176/ps.2009.60.11.1439.
- Background: PubMed 16390886Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006 Jan;163(1):28-40. doi: 10.1176/appi.ajp.163.1.28.
- Background: PubMed 24789696Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013. Psychiatr Serv. 2014 Aug 1;65(8):977-87. doi: 10.1176/appi.ps.201300059.
- Background: PubMed 14658951Papakostas GI, Petersen TJ, Farabaugh AH, Murakami JL, Pava JA, Alpert JE, Fava M, Nierenberg AA. Psychiatric comorbidity as a predictor of clinical response to nortriptyline in treatment-resistant major depressive disorder. J Clin Psychiatry. 2003 Nov;64(11):1357-61. doi: 10.4088/jcp.v64n1112.
- Background: PubMed 21734685Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS; Scientific Advisory Board and the Executive Committee of the Grand Challenges on Global Mental Health; Anderson W, Dhansay MA, Phillips A, Shurin S, Walport M, Ewart W, Savill SJ, Bordin IA, Costello EJ, Durkin M, Fairburn C, Glass RI, Hall W, Huang Y, Hyman SE, Jamison K, Kaaya S, Kapur S, Kleinman A, Ogunniyi A, Otero-Ojeda A, Poo MM, Ravindranath V, Sahakian BJ, Saxena S, Singer PA, Stein DJ. Grand challenges in global mental health. Nature. 2011 Jul 6;475(7354):27-30. doi: 10.1038/475027a. No abstract available.
- Background: PubMed 17444078Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry. 2007 Jan;52(1):46-54. doi: 10.1177/070674370705200108.
- Background: PubMed 25767082Sanacora G, Schatzberg AF. Ketamine: promising path or false prophecy in the development of novel therapeutics for mood disorders? Neuropsychopharmacology. 2015 Mar 13;40(5):1307. doi: 10.1038/npp.2014.338. No abstract available.
- Background: PubMed 25533726Chen C, Ji M, Xu Q, Zhang Y, Sun Q, Liu J, Zhu S, Li W. Sevoflurane attenuates stress-enhanced fear learning by regulating hippocampal BDNF expression and Akt/GSK-3beta signaling pathway in a rat model of post-traumatic stress disorder. J Anesth. 2015 Aug;29(4):600-8. doi: 10.1007/s00540-014-1964-x. Epub 2014 Dec 23.
- Background: PubMed 26991409Zhang H, Li L, Sun Y, Zhang X, Zhang Y, Xu S, Zhao P, Liu T. Sevoflurane prevents stroke-induced depressive and anxiety behaviors by promoting cannabinoid receptor subtype I-dependent interaction between beta-arrestin 2 and extracellular signal-regulated kinases 1/2 in the rat hippocampus. J Neurochem. 2016 May;137(4):618-29. doi: 10.1111/jnc.13613. Epub 2016 Mar 31.
- Background: PubMed 26400403Luo C, Zhang YL, Luo W, Zhou FH, Li CQ, Xu JM, Dai RP. Differential effects of general anesthetics on anxiety-like behavior in formalin-induced pain: involvement of ERK activation in the anterior cingulate cortex. Psychopharmacology (Berl). 2015 Dec;232(24):4433-44. doi: 10.1007/s00213-015-4071-2. Epub 2015 Sep 24.
- Background: PubMed 31368063Guo Z, Zhao F, Wang Y, Wang Y, Geng M, Zhang Y, Ma Q, Xu X. Sevoflurane Exerts an Anti-depressive Action by Blocking the HMGB1/TLR4 Pathway in Unpredictable Chronic Mild Stress Rats. J Mol Neurosci. 2019 Dec;69(4):546-556. doi: 10.1007/s12031-019-01380-2. Epub 2019 Jul 31.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhiqiang Liu, MD study chair
Department of Anesthesiaology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sevoflurane in people with Depressive Disorder, Treatment-Resistant and Depressive Disorder, Major, run by Shanghai First Maternity and Infant Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fuyi Shen, MD (86-13524123072, shenfuyi315@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rates of treatment responses in 17-item Hamilton Depression Rating Scale (HDRS-17) (time frame: 24 hours after the end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05008939, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2021.