Washed Microbiota Transplantation for Attention-deficit/Hyperactivity Disorder

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

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.

Study Overview

• Status: Recruiting
• Conditions: Attention-deficit/Hyperactivity Disorder
• Intervention / Treatment: Drug: washed microbiota transplantation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Faming Zhang, PhD; Phone Number: 086-25-58509883; Email: fzhang@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University
      • Contact: Faming Zhang, PhD; Phone Number: 086-025-58509883; Email: fzhang@njmu.edu.cn
    • Nanjing, Jiangsu, China
      • Recruiting
      • Sir Run Run Hospital of Nanjing Medical University
      • Contact: Faming Zhang, PhD; Phone Number: 086-25-58509883; Email: fzhang@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Washed microbiota transplantation; WMT	Drug: washed microbiota transplantation; The prepared microbiota suspension was infused into the participates' lower gut.; Other Names: fecal microbiota transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impressions-Improvement (CGI-I)	The Clinical Global Impressions-Improvement (CGI-I) evaluated by experienced clinician was used to assess the symptom changes relative to baseline, rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). CGI-I = 1 or 2 was considered a clinical response.	1 month, 3 months post transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of the Sleep Disturbance Scale for Children (SDSC).	The SDSC is 26-item test measuring sleep problems and each item receives a value from 1 to 5, with higher scores indicating more severe sleep disorders.	baseline, 1 month, 3 months post transplantation
change of the Gastrointestinal Symptom Rating Scale (GSRS) .	It is based on 15 questions which are scored into 5 domains: abdominal pain, reflux, indigestion, diarrhea, and constipation. Each item weights from 1 to 7, with higher scores reflecting more severe symptoms.	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.	The composition of the gut microbiota is evaluated by sequencing faecal metagenome. We evaluate the differences in the structure of the flora and its metabolism between the two at the phylum, genus and species levels of the intestinal flora and control children, and to develop a model for predicting the structure of the flora.	baseline, 1 month, 3 months post transplantation
intestinal barrier	plasma DAO, D-lactic acid and bacterial endotoxin levels	baseline, 1 month, 3 months post transplantation
change of Swanson, Nolan and Pelham-IV (SNAP-IV).	It is an 26-item questionnaire that measured three of the ADHD symptoms, inattention, hyperactivity and oppositional defiant disorder. The 26-item checklist is scored on a 4-point Likert scale ranging between Not At All (0) and Very Much (3).	baseline, 1 month, 3 months post transplantation
Conners' Parent Rating Scale-Revised	ADHD symptoms were also assessed by the Conners' Parent Rating Scale-Revised (CPRS-R). The CPRS-R was composed of 10 items derived from the Revised Conners Parent Rating Scale. It used a 4-point Likert scale (range: 0-30), with higher scores indicating more severe symptoms.	baseline, 1 month, 3 months post transplantation

Collaborators and Investigators

• Sponsor: The Second Hospital of Nanjing Medical University
• Collaborators: Nanjing Medical University
• Investigators: Principal Investigator: Faming Zhang, PhD, The Second Hospital of Nanjing Medical University

Publications and helpful links

General Publications

• Bussing R, Fernandez M, Harwood M, Wei Hou, Garvan CW, Eyberg SM, Swanson JM. Parent and teacher SNAP-IV ratings of attention deficit hyperactivity disorder symptoms: psychometric properties and normative ratings from a school district sample. Assessment. 2008 Sep;15(3):317-28. doi: 10.1177/1073191107313888. Epub 2008 Feb 29.
• Svedlund J, Sjodin I, Dotevall G. GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988 Feb;33(2):129-34. doi: 10.1007/BF01535722.
• 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.
• Goyette CH, Conners CK, Ulrich RF. Normative data on revised Conners Parent and Teacher Rating Scales. J Abnorm Child Psychol. 1978 Jun;6(2):221-36. doi: 10.1007/BF00919127.
• Bruni O, Ottaviano S, Guidetti V, Romoli M, Innocenzi M, Cortesi F, Giannotti F. The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence. J Sleep Res. 1996 Dec;5(4):251-61. doi: 10.1111/j.1365-2869.1996.00251.x.
• 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.
• 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.
• 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.
• 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. 2023 Aug;151:105209. doi: 10.1016/j.neubiorev.2023.105209. Epub 2023 May 5.
• 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.
• 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.
• 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.
• Nanjing consensus on methodology of washed microbiota transplantation. Chin Med J (Engl). 2020 Oct 5;133(19):2330-2332. doi: 10.1097/CM9.0000000000000954. No abstract available.
• Hooi SL, Dwiyanto J, Rasiti H, Toh KY, Wong RKM, Lee JWJ. A case report of improvement on ADHD symptoms after fecal microbiota transplantation with gut microbiome profiling pre- and post-procedure. Curr Med Res Opin. 2022 Nov;38(11):1977-1982. doi: 10.1080/03007995.2022.2129232. Epub 2022 Oct 7.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: fecal microbiota transplantation; gut-brain axis; sleep disturbance; attention-deficit/hyperactivity disorder; washed microbiota transplantation
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Neurodevelopmental Disorders; Attention Deficit and Disruptive Behavior Disorders; Parasomnias; Attention Deficit Disorder with Hyperactivity; Therapeutics; Biological Therapy; Fecal Microbiota Transplantation
• Other Study ID Numbers: ADHD20240403

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No