Washed Microbiota Transplantation for Tourette's Syndrome (WMT)

Efficacy and Safety of Washed Microbiota Transplantation for Tourette's Syndrome

This study aimed to evaluate the efficacy of washed microbiota transplantation in the treatment of Tourette's syndrome (TS).

Study Overview

• Status: Recruiting
• Conditions: Tourette Syndrome
• Intervention / Treatment: Drug: Washed Microbiota Transplantation

Detailed Description

Emerging scientific data support the significant role of microbiota in the modulation of the central nervous system. The reconstitution of gut microbiota might be a potential option to treat Tourette's syndrome (TS). 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 Tourette's syndrome. In this study, investigators aimed to evaluate the efficacy of WMT for Tourette's syndrome and its comorbidities using specialized questionnaires for Tourette's syndrome and investigate the underlying mechanism.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Faming Zhang, MD; PHD; Phone Number: 025-58509883; Email: fzhang@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • Recruiting
      • Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University
      • Contact: Faming Zhang, PhD,MD; Phone Number: 86-025-58509883; Email: fzhang@njmu.edu.cn
      • Principal Investigator: Faming Zhang, MD,PhD
    • Nanjing, Jiangsu, China, 210011
      • Recruiting
      • Sir Run Run Hospital of Nanjing Medical University
      • Contact: Faming Zhang, MD, PhD; Phone Number: 086-25-58509883; Email: fzhang@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 56 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Patients were aged 6 to 17 years (inclusive);
2. Met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for TS;
3. Had a Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) of at least 20 at screening and baseline.
4. Underwent WMT.

Exclusion Criteria:

1. Complicated with certain brain disease, including tumor,injury,cerebrovascular disease;
2. Complicated with other severe disease, including cancers, organ failure, heart diseases;
3. Stereotypy associated with autism spectrum disorder;
4. With a confirmed diagnosis of psychiatric diseases, such as bipolar disorders; schizophrenia and major depressive disorders;
5. Clinically significant obsessive-compulsive disorder at baseline considered to be the primary cause of impairment at baseline;
6. Medications use affecting gut microbiota such as antibiotics and probiotics three months before WMT.
7. Other neurologic disorders other than TS that could influence the evaluation of tics.

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
The change of Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS)	The YGTSS rating scale is a semistructured clinician- or investigator-administered rating instrument in which participants or caregivers evaluate the number, frequency, intensity, complexity, and interference of motor and phonic tics in the prior week on a 6-point scale from 0 (none) to 5 (severe) [1]. The total Motor Tic Severity Score (MTSS; 0-25 points) is added to the total Vocal Tic Severity Score (VTSS; 0-25 points) to determine the TTS (0-50 points).	baseline, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
the Clinical Global Impressions-Improvement scale	Positive treatment response was defined by a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions-Improvement scale. The Clinical Global Impression - Improvement scale is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as:1.Very much improved; 2.Much improved; 3. Minimally improved; 4. No change; 5. Minimally worse; 6. Much worse; 7.Very much worse.	4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
the change of Gilles de la Tourette Syndrome Quality-of-Life Scale score	The Gilles de la Tourette Syndrome Quality-of-Life Scale with 27 items addresses the issue of how the illness affects patients' well-being. It ranges from 0 to108, and higher values represent a worse outcome.	baseline, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
the change of The Swanson, Nolan, and Pelham IV Scale (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
change of the Sleep Disturbance Scale for Children (SDSC)	The SDSC was 26-item test measuring sleep problems and each item received a value from 0 to 4, with higher scores indicating more severe sleep disorders.	baseline, 4 weeks, 8 weeks, 12 weeks, 6 months post transplantation
the difference of the gut microbe composition between individuals with TS 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 individuals with TS and control children at the phylum, genus and species levels of the intestinal flora, and to develop a model for predicting the structure of the flora.	baseline, 12 weeks, 6 months post transplantation

Collaborators and Investigators

• Sponsor: The Second Hospital of Nanjing Medical University
• Collaborators: SIR RUN RUN hospital of Nanjing Medical University
• Investigators: Study Chair: Faming Zhang, MD; PHD, The Second Hospital of Nanjing Medical University

Publications and helpful links

General Publications

• Zhang F, Cui B, He X, Nie Y, Wu K, Fan D; FMT-standardization Study Group. Microbiota transplantation: concept, methodology and strategy for its modernization. Protein Cell. 2018 May;9(5):462-473. doi: 10.1007/s13238-018-0541-8. Epub 2018 Apr 24.
• Peng Z, Xiang J, He Z, Zhang T, Xu L, Cui B, Li P, Huang G, Ji G, Nie Y, Wu K, Fan D, Zhang F. Colonic transendoscopic enteral tubing: A novel way of transplanting fecal microbiota. Endosc Int Open. 2016 Jun;4(6):E610-3. doi: 10.1055/s-0042-105205. Epub 2016 Apr 28.
• Roessner V, Plessen KJ, Rothenberger A, Ludolph AG, Rizzo R, Skov L, Strand G, Stern JS, Termine C, Hoekstra PJ; ESSTS Guidelines Group. European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur Child Adolesc Psychiatry. 2011 Apr;20(4):173-96. doi: 10.1007/s00787-011-0163-7. Erratum In: Eur Child Adolesc Psychiatry. 2011 Jul;20(7):377.
• Hoffman BU, Lumpkin EA. A gut feeling. Science. 2018 Sep 21;361(6408):1203-1204. doi: 10.1126/science.aau9973. No abstract available.
• Foster JA. Targeting the Microbiome for Mental Health: Hype or Hope? Biol Psychiatry. 2017 Oct 1;82(7):456-457. doi: 10.1016/j.biopsych.2017.08.002. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: November 30, 2018
• First Submitted That Met QC Criteria: December 3, 2018
• First Posted (Actual): December 5, 2018

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Gut microbiota; Tourette syndrome; Tic Disorders; Brain-gut axis; Washed Microbiota Transplantation
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Syndrome; Tourette Syndrome
• Other Study ID Numbers: WMT-TS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No