Sustained Mood Improvement With Laughing Gas Exposure

Официальное название

Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Double-Blind Trial

Обзор

Multi-centre, parallel group, blinded, 1:1 randomized controlled trial to determine the effect of nitrous oxide on reducing symptoms of depression in patients with treatment resistant depression.

Подробное описание

SMILE is a multi-centre, parallel-group, blinded randomized controlled trial of 120 patients with treatment resistant depression. Consented eligible patients will be randomized to 1) Inhalation of Nitrous Oxide + Intravenous Saline (intervention Group)or 2) Inhalation of Oxygen + Intravenous Midazolam (Active Control Group). Participants will receive their respective study intervention once a week for four weeks for a total of four sessions. Follow-up visits will be conducted over the phone 2-weeks, 4-weeks, and 12-weeks following the last intervention visit. Questionnaires will be administered to assess change in depressive symptoms, function, and quality of life.

Вмешательства

• Препарат Inhalation of Nitrous oxide (Laughing gas) + intravenous saline
  Nitrous oxide at an inspiratory concentration of 50% with concurrent intravenous saline (20ml) for one hour.
• Препарат inhalation of %100 oxygen + intravenous midazolam
  Inspiration of 100% oxygen with concurrent intravenous midazolam (0.02mg/kg, up to 2 mg) for one hour.

Первичные конечные точки

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score [Срок оценки: Baseline to the 2-week follow-up (Visit 6 - Day 35).]

Вторичные конечные точки (8)

• Proportion of patients who achieved a response [Срок оценки: 2-week and 12-week follow-ups post last intervention visit]
• Proportion of patients who achieved remission [Срок оценки: 2-week and 12-week follow-ups post last intervention visit]
• Change in self-reported depressive symptoms [Срок оценки: 2-week and 12-week follow-ups post last intervention visit]
• Change in cognitive function [Срок оценки: 2-week and 12-week follow-ups post last intervention visit]
• Change in functioning and disability [Срок оценки: 2-week and 12-week follow-ups post last intervention visit]
• Change in anxiety symptoms [Срок оценки: 2-week and 12-week follow-ups post last intervention visit]
• Change in quality of life [Срок оценки: 2-week and 12-week follow-ups post last intervention visit]
• Assessment of Safety via FIBSER Scale [Срок оценки: Baseline to Week 12]

Критерии участия

Критерии включения

• 18 to 65 years of age
• Meeting Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for Major Depressive Disorder (MDD)
• Current major depressive episode as confirmed by the Mini International Neuropsychiatric Interview (MINI) for DSM-5
• Experiencing moderate to severe depressive episodes, as defined by the Montgomery-Åsberg Depression Rating Scale (MADRS) > 21
• Failure of two trials of antidepressant therapy of adequate dose and duration, during the current depressive episode
• For women of childbearing potential, use of highly effective or double-barrier methods of contraception. Abstinence is acceptable if it is the preferred and usual lifestyle of the female participant
• Capacity to provide informed consent.

Критерии исключения

• Acute suicidality defined as score > 4 on MADRS item 10
• Diagnosis of Bipolar Disorder
• Current substance abuse or dependence and/or history of alcohol abuse or dependence within the past year
• Dementia
• Current or lifetime history of schizophrenia or schizoaffective disorder
• Known history of hypersensitivity or allergy to nitrous oxide, midazolam or any ingredients in the study formulations
• Contraindication to receiving nitrous oxide (e.g. any condition where air is entrapped within a body and its expansion might be dangerous such as, pneumothorax, elevated intracranial pressure, air embolism, recent middle ear, vitreoretinal or bowel obstruction surgeries, etc.)
• Known chronic cobalamin or folate deficiency (e.g. signs of anemia or neurological symptoms, with plasma levels of homocysteine over 15 µmol/L and abnormal red blood cells and leukocytes on a complete blood count CBC) or current methotrexate use
• Contraindication to receiving the placebo midazolam (e.g. shock, chronic heart failure, chronic obstructive pulmonary disease, closed-angle glaucoma, renal failure, patients with limited pulmonary reserve or those with severe decline of vital signs)
• Daily use of centrally acting medicinal products, such as opioid agonists, (e.g. naloxone and naltrexone) morphine derivatives (e.g. oxycodone, hydrocodone, oxymorphone, codeine), benzodiazepines (e.g. diazepam, clonazepam, alprazolam) and/or other central nervous system depressants such as barbiturates (e.g. phenobarbital, pentobarbital, amobarbital) and alcohol within the past week.
• Pregnancy or breastfeeding
• Received electroconvulsive therapy within the past six months
• Received ketamine treatment within the past six months
• Received repetitive transcranial magnetic stimulation within the past six months
• Unwilling to maintain current antidepressant regimen.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Канада · 5 центров

• Sunnybrook Health Sciences Centre — Toronto
• St. Michael's Hospital (Unity Health) — Toronto
• Toronto General Hospital (UHN) — Toronto
• Women's College Hospital — Toronto
• Toronto Western Hospital (UHN) — Toronto

Публикации

• Ladha KS, Lee J, Mattina GF, Pazmino-Canizares J, Wijeysundera DN, Nezhad FG, Tassone VK, Adamsahib F, Lou W, Kennedy S, Bhat V; SMILE Study Investigators. Sustained mood improvement with laughing gas exposure (SMILE): a randomised, placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression. BJPsych Open. 2025 Sep 12;11(5):e208. doi: 10.1192/bjo.2025.10823. PMID 40936464

Идентификаторы

NCT: NCT07262008 · 5428-CTO

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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