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Effect of Psilocybin and Structured Integrated Reframing Therapy on Gut-Brain Axis Biomarkers and Depression in Major Depressive Disorder

12. července 2026 aktualizováno: Khyber Medical University Peshawar

Effect of Psilocybin and Structured Integrated Reframing Therapy on Gut-Brain Axis Biomarkers and Depression in Trauma-Related Major Depressive Disorder: Randomized Controlled Trial

Trauma-related Major Depressive Disorder (MDD) is frequently associated with poor response to conventional antidepressants, persistent psychological distress, and alterations in gut-brain axis function. Existing assessment tools primarily diagnose depression or PTSD but provide limited guidance for integrated clinical management. This study aims to develop and validate the Trauma Anxiety Depression Emotion (TADE) management tool while simultaneously evaluating the effectiveness of psilocybin-assisted Structured Integrated Reframing Therapy (SIRT) in improving clinical and biological outcomes.

This prospective, four-arm randomized controlled trial will compare conventional therapy, psilocybin therapy, SIRT, and psilocybin-assisted SIRT. Participants will undergo assessment using the newly developed TADE tool together with established psychometric scales including HAM-D, PCL-5, and GAD-7. Biological outcomes will include serum gut-brain axis and inflammatory biomarkers, including Short-Chain Fatty Acids (SCFAs), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Zonulin, Occludin, and Glial Cell Line-Derived Neurotrophic Factor (GDNF). Assessments will be performed at baseline, during treatment, and at 12-week follow-up. The study aims to determine whether combining psilocybin with SIRT provides superior clinical improvement and favorable biological changes compared with either intervention alone while establishing the validity and clinical utility of the TADE management tool.

Přehled studie

Postavení

Nábor

Podmínky

Intervence / Léčba

Detailní popis

Major Depressive Disorder (MDD) is among the leading causes of disability worldwide. Individuals with trauma-related MDD frequently experience persistent depressive symptoms, anxiety, emotional dysregulation, post-traumatic stress symptoms, and impaired quality of life despite receiving conventional antidepressant therapy. Emerging evidence suggests that gut microbiota, intestinal permeability, immune activation, neuroplasticity, and inflammatory pathways contribute significantly to the pathophysiology of depression and trauma-related disorders.

This study integrates two novel innovations. First, it will develop and validate the Trauma Anxiety Depression Emotion (TADE) management tool, a comprehensive instrument designed to assess trauma exposure, PTSD symptoms, depression, anxiety, stress, emotional functioning, and treatment priorities. Second, it will evaluate Structured Integrated Reframing Therapy (SIRT), a newly developed psychotherapy integrating Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), mindfulness, cognitive reframing, and communication-focused therapeutic techniques.

The study is designed as a prospective, four-arm, parallel-group randomized controlled trial. Eligible participants with trauma-related Major Depressive Disorder will be randomly allocated to one of four intervention groups: (1) conventional therapy, (2) psilocybin therapy, (3) Structured Integrated Reframing Therapy (SIRT), or (4) psilocybin-assisted SIRT.

Clinical outcomes will be evaluated using the TADE tool together with validated psychometric instruments including the Hamilton Depression Rating Scale (HAM-D), PTSD Checklist for DSM-5 (PCL-5), and Generalized Anxiety Disorder-7 (GAD-7). Biological outcomes will include measurement of gut-brain axis and inflammatory biomarkers including Short-Chain Fatty Acids (SCFAs), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Zonulin, Occludin, and Glial Cell Line-Derived Neurotrophic Factor (GDNF). Blood samples will be collected at baseline, Week 4, Week 8, and Week 12.

The primary objectives are to determine the effectiveness of psilocybin-assisted SIRT in reducing depressive symptoms and to validate the TADE management tool. Secondary objectives include evaluating changes in gut-brain axis biomarkers, determining correlations between biomarker changes and clinical improvement, and identifying biological predictors of treatment response. This integrated approach aims to provide evidence for a personalized treatment strategy that combines innovative psychotherapeutic interventions, psychedelic-assisted therapy, and biomarker-guided clinical management for trauma-related Major Depressive Disorder.

Typ studie

Intervenční

Zápis (Odhadovaný)

60

Fáze

  • Fáze 3

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

Studijní záloha kontaktů

Studijní místa

  • Pákistán
    • Capital
      • Islamabad, Capital, Pákistán, 25000
        • Aktivní, ne nábor
        • Institute of Health Science, Khyber Medical University
    • KPK
      • Peshawar, KPK, Pákistán, 25000
        • Nábor
        • Hayatabad Medical Complex Peshawar
        • Kontakt:
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Dr Owais Qaiser, PhD*
      • Peshawar, KPK, Pákistán
        • Aktivní, ne nábor
        • Khyber Medical University

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dospělý

Přijímá zdravé dobrovolníky

Ne

Popis

Inclusion Criteria:

  • Adults aged 18-60 years.
  • Diagnosis of Major Depressive Disorder (MDD) according to DSM-5 criteria.
  • Trauma-related depression with clinically significant trauma symptoms.
  • Hamilton Depression Rating Scale (HAM-D) score >16.
  • PTSD Checklist for DSM-5 (PCL-5) score >33.
  • Generalized Anxiety Disorder-7 (GAD-7) score >10.
  • Receiving a stable single SSRI antidepressant regimen for at least 6 weeks before enrollment with adequate treatment adherence.
  • Able and willing to provide written informed consent.
  • Willing to comply with all study procedures and follow-up visits.
  • Women of childbearing potential must agree to use effective contraception throughout the study.

Exclusion Criteria:

  • Significant cardiovascular disease.
  • Clinically significant hepatic or renal impairment.
  • Significant neurological disorders.
  • Current or past psychotic disorder or bipolar disorder.
  • Current substance or alcohol use disorder, including ketamine or psychedelic drug use.
  • Use of more than one antidepressant medication.
  • Pregnancy, planned pregnancy, or breastfeeding.
  • Known hypersensitivity or contraindication to psilocybin.
  • Participation in another interventional clinical trial within the previous 30 days.
  • Inability or unwillingness to provide informed consent.
  • Any medical or psychiatric condition that, in the investigator's opinion, would interfere with safe participation or study assessments.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Aktivní komparátor: Conventional Therapy (Control)
Participants will receive standard conventional treatment for trauma-related Major Depressive Disorder, consisting of a stable selective serotonin reuptake inhibitor (SSRI) regimen prescribed by the treating psychiatrist. No psilocybin or Structured Integrated Reframing Therapy (SIRT) will be administered. Treatment will continue for 8 weeks with routine clinical follow-up.
Lék: Selective Serotonin Reuptake Inhibitor (SSRI)
Participants in all study arms will continue a stable prescribed selective serotonin reuptake inhibitor (SSRI) regimen throughout the study. Participants must have been receiving the same antidepressant for at least 6 weeks before enrollment with adequate treatment adherence. Medication adjustments will be made only if clinically indicated.
Ostatní jména:
  • Standard antidepressant therapy
Experimentální: Psilocybin Therapy
Participants will continue standard SSRI therapy and receive oral psilocybin administered under medical supervision in a controlled clinical setting. Two supervised dosing sessions will be conducted during the 8-week intervention period according to the study protocol. No SIRT will be provided.
Lék: Selective Serotonin Reuptake Inhibitor (SSRI)
Participants in all study arms will continue a stable prescribed selective serotonin reuptake inhibitor (SSRI) regimen throughout the study. Participants must have been receiving the same antidepressant for at least 6 weeks before enrollment with adequate treatment adherence. Medication adjustments will be made only if clinically indicated.
Ostatní jména:
  • Standard antidepressant therapy
Lék: Psilocybin
Oral psilocybin administered under medical supervision in a controlled clinical setting. Participants assigned to psilocybin-containing arms will receive two supervised dosing sessions during the 8-week intervention period in addition to stable standard antidepressant therapy. The dosage and administration procedures will follow the approved study protocol.
Experimentální: Structured Integrated Reframing Therapy (SIRT)
Participants will continue standard SSRI therapy and receive Structured Integrated Reframing Therapy (SIRT), a trauma-informed psychotherapy integrating Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), mindfulness, cognitive reframing, and communication-focused therapeutic techniques. Therapy will be delivered once weekly for 8 weeks by trained therapists.
Lék: Selective Serotonin Reuptake Inhibitor (SSRI)
Participants in all study arms will continue a stable prescribed selective serotonin reuptake inhibitor (SSRI) regimen throughout the study. Participants must have been receiving the same antidepressant for at least 6 weeks before enrollment with adequate treatment adherence. Medication adjustments will be made only if clinically indicated.
Ostatní jména:
  • Standard antidepressant therapy
Behaviorální: Structured Integrated Reframing Therapy (SIRT)
Structured Integrated Reframing Therapy (SIRT) is a trauma-informed psychotherapy integrating evidence-based components of Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), mindfulness, cognitive reframing, emotional regulation, coping skills training, and communication-focused therapeutic techniques. Therapy is delivered once weekly for 8 weeks by trained therapists.
Experimentální: Psilocybin-Assisted Structured Integrated Reframing Therapy
Participants will continue standard SSRI therapy and receive both supervised oral psilocybin administration and Structured Integrated Reframing Therapy (SIRT). Psilocybin will be administered in two supervised dosing sessions during the 8-week intervention period, while SIRT will be delivered once weekly for 8 weeks. The combined intervention is intended to evaluate the synergistic effects of psychedelic-assisted psychotherapy on clinical outcomes and gut-brain axis biomarkers.
Lék: Selective Serotonin Reuptake Inhibitor (SSRI)
Participants in all study arms will continue a stable prescribed selective serotonin reuptake inhibitor (SSRI) regimen throughout the study. Participants must have been receiving the same antidepressant for at least 6 weeks before enrollment with adequate treatment adherence. Medication adjustments will be made only if clinically indicated.
Ostatní jména:
  • Standard antidepressant therapy
Lék: Psilocybin
Oral psilocybin administered under medical supervision in a controlled clinical setting. Participants assigned to psilocybin-containing arms will receive two supervised dosing sessions during the 8-week intervention period in addition to stable standard antidepressant therapy. The dosage and administration procedures will follow the approved study protocol.
Behaviorální: Structured Integrated Reframing Therapy (SIRT)
Structured Integrated Reframing Therapy (SIRT) is a trauma-informed psychotherapy integrating evidence-based components of Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), mindfulness, cognitive reframing, emotional regulation, coping skills training, and communication-focused therapeutic techniques. Therapy is delivered once weekly for 8 weeks by trained therapists.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Depression Severity
Časové okno: Baseline, Week 4, Week 8, and Week 12
Change in depression severity measured using the Hamilton Depression Rating Scale (HAM-D-17). The HAM-D-17 is a clinician-administered scale with a total score ranging from 0 to 52, where higher scores indicate more severe depressive symptoms. The outcome will be reported as the change in total HAM-D-17 score from baseline.
Baseline, Week 4, Week 8, and Week 12
Trauma-Related Symptoms
Časové okno: Baseline, Week 4, Week 8, and Week 12
Change in trauma-related symptoms measured using the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5). The PCL-5 is a self-report questionnaire with a total score ranging from 0 to 80, where higher scores indicate more severe PTSD symptoms. The outcome will be reported as the change in total PCL-5 score from baseline.
Baseline, Week 4, Week 8, and Week 12
Anxiety Severity
Časové okno: Baseline, Week 4, Week 8, and Week 12
Change in anxiety severity measured using the Generalized Anxiety Disorder 7-item Scale (GAD-7). The GAD-7 is a self-report questionnaire with a total score ranging from 0 to 21, where higher scores indicate more severe anxiety symptoms. The outcome will be reported as the change in total GAD-7 score from baseline.
Baseline, Week 4, Week 8, and Week 12
Gut-Brain Axis and Neuroinflammatory Biomarkers
Časové okno: Baseline, Week 4, Week 8, and Week 12

Change in serum concentrations of gut-brain axis and neuroinflammatory biomarkers, including:

Short-Chain Fatty Acids (SCFAs) Interleukin-6 (IL-6) Interleukin-10 (IL-10) Zonulin Occludin Glial Cell Line-Derived Neurotrophic Factor (GDNF)

Biomarkers will be quantified using validated laboratory assays and reported in their respective concentration units (e.g., pg/mL or ng/mL, as appropriate).
Baseline, Week 4, Week 8, and Week 12

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Khyber Medical University Peshawar

Spolupracovníci

Hayatabad Medical Complex
KMU Institute of Health Science, Islamabad

Vyšetřovatelé

  • Vrchní vyšetřovatel: Dr Omer Malik, PhD, Khyber Medical University Peshawar, Pakistan
  • Studijní židle: Dr Inayat Shah, PhD*, Khyber Medical University
  • Vrchní vyšetřovatel: Naveeda Sarwar, PhD, Khyber Medical University

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

1. dubna 2026

Primární dokončení (Odhadovaný)

22. října 2027

Dokončení studie (Odhadovaný)

22. listopadu 2027

Termíny zápisu do studia

První předloženo

6. července 2026

První předloženo, které splnilo kritéria kontroly kvality

12. července 2026

První zveřejněno (Aktuální)

14. července 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

14. července 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

12. července 2026

Naposledy ověřeno

1. července 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • KMU/DIR/CTU/2026/6

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu IPD

Individual Participant Data (IPD) that underlie the results reported in publications, including de-identified demographic, clinical, psychometric, and biomarker data, will be made available to qualified researchers upon reasonable request. Data will be shared after publication of the primary study results, subject to approval by the Principal Investigator and Khyber Medical University Institutional Research Ethics Board. All shared data will be de-identified to protect participant confidentiality.

Časový rámec sdílení IPD

Data will become available within 6 months after publication of the primary study results and will remain available for 5 years thereafter.

Kritéria přístupu pro sdílení IPD

Qualified researchers may request access by submitting a methodologically sound research proposal. Requests will be reviewed by the Principal Investigator and the Khyber Medical University Institutional Research Ethics Board. A data access agreement may be required before de-identified data are released.

Typ podpůrných informací pro sdílení IPD

  • PROTOKOL STUDY
  • MÍZA
  • ICF

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

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