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

12 lipca 2026 zaktualizowane przez: 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.

Przegląd badań

Status

Rekrutacyjny

Warunki

Interwencja / Leczenie

Szczegółowy opis

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 studiów

Interwencyjne

Zapisy (Szacowany)

60

Faza

  • Faza 3

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Kopia zapasowa kontaktu do badania

Lokalizacje studiów

  • Pakistan
    • Capital
      • Islamabad, Capital, Pakistan, 25000
        • Aktywny, nie rekrutujący
        • Institute of Health Science, Khyber Medical University
    • KPK
      • Peshawar, KPK, Pakistan, 25000
        • Rekrutacyjny
        • Hayatabad Medical Complex Peshawar
        • Kontakt:
        • Kontakt:
        • Główny śledczy:
          • Dr Owais Qaiser, PhD*
      • Peshawar, KPK, Pakistan
        • Aktywny, nie rekrutujący
        • Khyber Medical University

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dorosły

Akceptuje zdrowych ochotników

Nie

Opis

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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Aktywny komparator: 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.
Lek: 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.
Inne nazwy:
  • Standard antidepressant therapy
Eksperymentalny: 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.
Lek: 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.
Inne nazwy:
  • Standard antidepressant therapy
Lek: 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.
Eksperymentalny: 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.
Lek: 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.
Inne nazwy:
  • Standard antidepressant therapy
Behawioralne: 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.
Eksperymentalny: 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.
Lek: 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.
Inne nazwy:
  • Standard antidepressant therapy
Lek: 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.
Behawioralne: 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 mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Depression Severity
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Khyber Medical University Peshawar

Współpracownicy

Hayatabad Medical Complex
KMU Institute of Health Science, Islamabad

Śledczy

  • Główny śledczy: Dr Omer Malik, PhD, Khyber Medical University Peshawar, Pakistan
  • Krzesło do nauki: Dr Inayat Shah, PhD*, Khyber Medical University
  • Główny śledczy: Naveeda Sarwar, PhD, Khyber Medical University

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

1 kwietnia 2026

Zakończenie podstawowe (Szacowany)

22 października 2027

Ukończenie studiów (Szacowany)

22 listopada 2027

Daty rejestracji na studia

Pierwszy przesłany

6 lipca 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

12 lipca 2026

Pierwszy wysłany (Rzeczywisty)

14 lipca 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

14 lipca 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

12 lipca 2026

Ostatnia weryfikacja

1 lipca 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • KMU/DIR/CTU/2026/6

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu 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.

Ramy czasowe udostępniania IPD

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

Kryteria dostępu do udostępniania 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 informacji pomocniczych dotyczących udostępniania IPD

  • PROTOKÓŁ BADANIA
  • SOK ROŚLINNY
  • ICF

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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