Washed Microbiota Transplantation for Attention-deficit/Hyperactivity Disorder

Официальное название

Washed Microbiota Transplantation for Attention-deficit/Hyperactivity Disorder and Its Comorbidities

Обзор

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention and hyperactivity-impulsivity. ADHD is often accompanied by oppositional defiant disorder and sleep disturbance, and can increase the risk of other psychiatric disorders, functional impairment in academic and occupational performance. Recently, gut microbiota has been implicated in the ADHD via gut-brain axis. In this study, investigators aimed to evaluate the efficacy of WMT for core ADHD symptoms and its comorbidities using specialized questionnaires for ADHD and investigate the underlying mechanism.

Подробное описание

Gut microbiota dysbiosis has been reported to play a critical role in the initiation and progression of neurodevelopmental disorders like ADHD via the gut-brain axis. Therapies targeting gut microbiota including including probiotics, prebiotics and fecal microbiota transplantation (FMT) might provide new insight into the management of ADHD. FMT has been reported to be a highly effective therapy to restore the gut microbiota dysbiosis by transferring gut microbiota from healthy donors to patients. The newly improved methodology of FMT based on the automatic washing process and the related delivering consideration was named as washed microbiota transplantation (WMT) by the FMT-standardization study group. FMT has shown treatment potential in several gut-brain axis-related disorders, such as amyotrophic lateral sclerosis and Parkinson's disease, promoting us to investigate its treatment potential for ADHD and its comorbidities. To date, only one case report showed a 22-year-old woman undergoing FMT primarily to treat recurrent Clostridioides difficile infection achieved ADHD symptoms alleviation. However, the efficacy of WMT for ADHD and the underlying mechanisms remain largely unexplored. In this study, investigators aimed to evaluate the efficacy of WMT for core ADHD symptoms and its comorbidities using specialized questionnaires for ADHD and investigate the underlying mechanism.

Вмешательства

• Препарат washed microbiota transplantation
  The prepared microbiota suspension was infused into the participates' lower gut.

Первичные конечные точки

• Clinical Global Impressions-Improvement (CGI-I) [Срок оценки: 1 month, 3 months post transplantation]

Вторичные конечные точки (6)

• change of the Sleep Disturbance Scale for Children (SDSC). [Срок оценки: baseline, 1 month, 3 months post transplantation]
• change of the Gastrointestinal Symptom Rating Scale (GSRS) . [Срок оценки: baseline, 1 month, 3 months post transplantation]
• the difference of the gut microbe composition between children with ADHD and healthy children by sequencing faecal metagenome. [Срок оценки: baseline, 1 month, 3 months post transplantation]
• intestinal barrier [Срок оценки: baseline, 1 month, 3 months post transplantation]
• change of Swanson, Nolan and Pelham-IV (SNAP-IV). [Срок оценки: baseline, 1 month, 3 months post transplantation]
• Conners' Parent Rating Scale-Revised [Срок оценки: baseline, 1 month, 3 months post transplantation]

Критерии участия

Критерии включения

• Children with an established diagnosis of ADHD according to Diagnostic And Statistical Manual Of Mental Disorders Fifth Edition;
• Aged 3-17;
• Received stable treatments for ≥1 month preceding WMT;
• Did not take medications affecting gut microbiota such as antibiotics and probiotics three months before WMT.

Критерии исключения

• Unable to understand the questionnaires or provide informed consent by the guardian;
• Diagnosed with a single-gene disorder, psychosis, central nervous system diseases, gastrointestinal diseases including ulcerative colitis, Crohn's disease, celiac disease, or eosinophilic esophagitis;
• Had severe comorbidities including cardiopulmonary failure, severe liver, and kidney diseases and cancer;
• Accompanied with other life-threatening disorders required emergency treatment;
• Unable to tolerate colonoscopy or anesthesia

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affi — Нанкин
• SIR RUN RUN hospital of Nanjing Medical University — Нанкин

Публикации

• Faraone SV, Bellgrove MA, Brikell I, Cortese S, Hartman CA, Hollis C, Newcorn JH, Philipsen A, Polanczyk GV, Rubia K, Sibley MH, Buitelaar JK. Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers. 2024 Feb 22;10(1):11. doi: 10.1038/s41572-024-00495-0. PMID 38388701
• Bansal PS, Goh PK, Southward MW, Sizemore YJ, Martel MM. Impulsivity as key bridge symptoms in cross-sectional and longitudinal networks of ADHD and ODD. J Child Psychol Psychiatry. 2024 Jan;65(1):52-63. doi: 10.1111/jcpp.13863. Epub 2023 Jul 20. PMID 37474723
• Liang X, Qiu H, Li SX. Objectively measured sleep continuity in children and adolescents with ADHD: A systematic review and meta-analysis. Psychiatry Res. 2023 Oct;328:115447. doi: 10.1016/j.psychres.2023.115447. Epub 2023 Aug 28. PMID 37657199
• Hartman CA, Larsson H, Vos M, Bellato A, Libutzki B, Solberg BS, Chen Q, Du Rietz E, Mostert JC, Kittel-Schneider S, Cormand B, Ribases M, Klungsoyr K, Haavik J, Dalsgaard S, Cortese S, Faraone SV, Reif A. Anxiety, mood, and substance use disorders in adult men and women with and without attention-deficit/hyperactivity disorder: A substantive and methodological overview. Neurosci Biobehav Rev. 202 PMID 37149075
• Wang Q, Yang Q, Liu X. The microbiota-gut-brain axis and neurodevelopmental disorders. Protein Cell. 2023 Oct 25;14(10):762-775. doi: 10.1093/procel/pwad026. PMID 37166201
• Tengeler AC, Dam SA, Wiesmann M, Naaijen J, van Bodegom M, Belzer C, Dederen PJ, Verweij V, Franke B, Kozicz T, Arias Vasquez A, Kiliaan AJ. Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice. Microbiome. 2020 Apr 1;8(1):44. doi: 10.1186/s40168-020-00816-x. PMID 32238191
• Elhossiny RM, Elshahawy HH, Mohamed HM, Abdelmageed RI. Assessment of probiotic strain Lactobacillus acidophilus LB supplementation as adjunctive management of attention-deficit hyperactivity disorder in children and adolescents: a randomized controlled clinical trial. BMC Psychiatry. 2023 Nov 9;23(1):823. doi: 10.1186/s12888-023-05324-4. PMID 37946220
• Zhang T, Lu G, Zhao Z, Liu Y, Shen Q, Li P, Chen Y, Yin H, Wang H, Marcella C, Cui B, Cheng L, Ji G, Zhang F. Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening. Protein Cell. 2020 Apr;11(4):251-266. doi: 10.1007/s13238-019-00684-8. Epub 2020 Jan 9. PMID 31919742

Идентификаторы

NCT: NCT06376331 · ADHD20240403

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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