Allopregnanolone (Zuranolone) in Post-stroke Depression

Обзор

The goal of this Phase II clinical trial is to learn if the oral synthetic allopreganolone analog (zuranolone) is safe to take and is well tolerated by stroke survivors experiencing moderate to severe post-stroke depression and if it will help with the symptoms of depression. The main questions it will aim to answer are: * Is zuranolone safe to take by participants who have moderate to severe post-stroke depression? * Is zuranolone well-tolerated by participants who have moderate to severe post-stroke depression? * Does zuranolone treat moderate to severe post-stroke depression? The study will enroll six participants. All participants will be given 50 mg of zuranolone for 14 days. Participants will be asked to provide blood samples, complete some questionnaires including those related to mood and a cognitive assessment.

Вмешательства

• Препарат Zuranolone
  Zuranolone is a neuroactive steroid that works by modulating the activity of the gamma-aminobutyric acid (GABA) receptor in the brain.

Первичные конечные точки

• Number of participants with treatment emergent adverse events (TEAEs) after starting zuranolone [Срок оценки: 90 days]
• Severity of suicidal ideation after starting zuranolone as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) [Срок оценки: 90 Days]
• Severity of somnolence after starting zuranolone as measured by the Epworth Sleepiness Scale (ESS) [Срок оценки: 90 Days]

Вторичные конечные точки (4)

• Change from baseline in Hamilton Depression Rating Scale (HAM-D) score at days 15 and 90 [Срок оценки: Baseline, 15 days, 90 days]
• Change from baseline in Hamilton Anxiety Rating Scale (HAM-A) score at days 15 and 90 [Срок оценки: Baseline, 15 days, 90 days]
• Number of participants with HAM-D response at 3, 15, and 90 days [Срок оценки: 3 days, 15 days, 90 days]
• Number of participants with HAM-D remission (score ≤7) rates at 3, 15, and 90 days [Срок оценки: 3 days, 15 days, 90 days]

Критерии участия

Критерии включения

• 21-65 years old of any sex and race/ethnicity
• Clinical ischemic or hemorrhagic acute stroke (confirmed by CT or MRI) occurring within 1 year of date of enrollment
• Moderate to severe PSD (Post-Stroke Depression) defined as having depressive symptoms lasting for at least 2 weeks and scoring 17 or more on the HAM-D (Hamilton Depression Rating Scale)

Критерии исключения

• Have abused or been dependent on narcotics, recreational drug use, or alcohol
• Advanced liver or kidney problems
• Pregnant or plan to become pregnant
• Post-partum period or breastfeeding
• History of attempted suicide
• Active psychosis or suicidal ideation necessitating clinical intervention
• Antidepressant medications titration or initiation within 12 weeks of recruitment
• History of Bipolar disorder, schizophrenia or treatment resistant depression preceding the stroke

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Duke South Neurology Clinic 1L — Durham

Публикации

• Wang S, Zhang W, Liu Z, Zhang T, Wang Y, Li W. Efficacy and safety of zuranolone in the treatment of major depressive disorder: a meta-analysis. Front Neurosci. 2024 Jan 16;17:1332329. doi: 10.3389/fnins.2023.1332329. eCollection 2023. PMID 38292895
• Clayton AH, Lasser R, Parikh SV, Iosifescu DV, Jung J, Kotecha M, Forrestal F, Jonas J, Kanes SJ, Doherty J. Zuranolone for the Treatment of Adults With Major Depressive Disorder: A Randomized, Placebo-Controlled Phase 3 Trial. Am J Psychiatry. 2023 Sep 1;180(9):676-684. doi: 10.1176/appi.ajp.20220459. Epub 2023 May 3. PMID 37132201
• Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, Doherty J, Jonas J, Li S, Sankoh AJ, Silber C, Campbell AD, Werneburg B, Kanes SJ, Lasser R. Effect of Zuranolone vs Placebo in Postpartum Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2021 Sep 1;78(9):951-959. doi: 10.1001/jamapsychiatry.2021.1559. PMID 34190962
• Sripada RK, Marx CE, King AP, Rampton JC, Ho SS, Liberzon I. Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits. Biol Psychiatry. 2013 Jun 1;73(11):1045-53. doi: 10.1016/j.biopsych.2012.12.008. Epub 2013 Jan 21. PMID 23348009
• Chen S, Gao L, Li X, Ye Y. Allopregnanolone in mood disorders: Mechanism and therapeutic development. Pharmacol Res. 2021 Jul;169:105682. doi: 10.1016/j.phrs.2021.105682. Epub 2021 May 18. PMID 34019980
• Pinna G, Almeida FB, Davis JM. Allopregnanolone in Postpartum Depression. Front Glob Womens Health. 2022 Apr 26;3:823616. doi: 10.3389/fgwh.2022.823616. eCollection 2022. PMID 35558166
• Diviccaro S, Cioffi L, Falvo E, Giatti S, Melcangi RC. Allopregnanolone: An overview on its synthesis and effects. J Neuroendocrinol. 2022 Feb;34(2):e12996. doi: 10.1111/jne.12996. Epub 2021 Jun 29. PMID 34189791
• Chen S, Wang T, Yao J, Brinton RD. Allopregnanolone Promotes Neuronal and Oligodendrocyte Differentiation In Vitro and In Vivo: Therapeutic Implication for Alzheimer's Disease. Neurotherapeutics. 2020 Oct;17(4):1813-1824. doi: 10.1007/s13311-020-00874-x. PMID 32632771

Идентификаторы

NCT: NCT06759558 · Pro00118406

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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