Washed Microbiota Transplantation for Attention-deficit/Hyperactivity Disorder

Attention-deficit/Hyperactivity Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06376331
• Other study ID #: ADHD20240403
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 20, 2024
• Est. completion date: July 1, 2027

Study information

• Verified date: April 2024
• Source: The Second Hospital of Nanjing Medical University
• Contact: Faming Zhang, PhD
• Phone: 086-25-58509883
• Email: fzhang[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: July 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

1. Children with an established diagnosis of ASD according to Diagnostic And Statistical Manual Of Mental Disorders Fifth Edition;

2. Aged 6-17;

3. Underwent 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. Used to undergo FMT in other medical centers;

6. Unable to tolerate colonoscopy or anesthesia

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention-deficit/Hyperactivity Disorder
• Hyperkinesis

Intervention

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

Locations

Country	Name	City	State
China	Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	SIR RUN RUN hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
The Second Hospital of Nanjing Medical University	SIR RUN RUN hospital of Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (14)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
Primary	change of Chinese version of the Conners abbreviated symptom questionnaire (C-ASQ).	The C-ASQ is composed of 10-item which derived from the Revised Conners Parent Rating Scale. It uses a 4-point Likert scale from 0 to 3 for children aged 3-17 years. It has been used as an effective screening instrument to identify and measure ADHD behavioural problems in Chinese children.	baseline, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
Secondary	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, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
Secondary	change of the Gastrointestinal Symptom Rating Scale (GSRS) .	It is based on 15 questions which are scored into 5 domains: abdominal pain, re?ux, indigestion, diarrhea, and constipation. Each item weights from 1 to 7, with higher scores reflecting more severe symptoms.	baseline, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
Secondary	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, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
Secondary	the difference of the serum neurotransmitters between children with ADHD and healthy children	The serum neurotransmitters is measured by high performance liquid chromatography-mass spectrometry.	baseline, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
Secondary	intestinal barrier	plasma DAO, D-lactic acid and bacterial endotoxin levels	baseline, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation