Starting soon
Phase 2
A Clinical Trial Evaluating Fecal Microbiota Transplantation (FMT) in Adolescents With ADHD
Condition(s) studied
ADHDADHD - Attention Deficit Disorder With HyperactivityADHD - Combined Type
Investigational drug(s) / intervention(s)
Fecal Microbiota Transplant (FMT): Participants will receive active oral FMT capsules, administered over three consecutive visits with each dose spaced 24 hours apart (20 capsules per visit at Visits 3A, 3B, and 3C). This will be administered following bowel preparation to serve as the primary therapeutic intervention for the active FMT regimen.
Nitazoxanide 500mg BID: Participants will receive oral combination therapy consisting of Nitazoxanide (500 mg administered in capsule form) taken twice daily for 6 consecutive days, administered concurrently with oral liquid Vancomycin (250 mg) twice daily for 6 days prior to dosing.
Vancomycin 250mg BID: Participants will receive oral liquid Vancomycin at a dose of 250 mg, administered twice daily for 6 consecutive days. This will be taken concurrently with oral Nitazoxanide capsules (500 mg) as part of FMT pre-treatment. Placebo antibiotic receiving participants will receive a matching oral liquid vehicle placebo on the identical twice-daily, 6-day schedule.
Placebo Vancomycin: Participants will receive a matching oral liquid vehicle placebo, administered twice daily for 6 consecutive days.
Placebo Nitazoxanide: Participants will receive matching oral placebo capsules, administered twice daily for 6 consecutive days.
Pico-Salax: Participants will undergo bowel cleansing prior to the intervention. On the evening before the first day of dosing participants will consume 1.5 sachets of Pico-Salax mixed in water, followed by eight 250 mL glasses of water over the subsequent 60 minutes to induce a bowel purge over an expected 6- to 8-hour period.
Placebo Fecal Microbiota Transplantation (FMT): Participants will receive matching oral placebo capsules, administered over three consecutive visits with each dose spaced 24 hours apart (20 capsules per visit at Visits 3A, 3B, and 3C). This will be administered following bowel preparation to serve as the control comparator for the active FMT regimen.
Study summary
The primary goals of this phase 2 clinical trial are to determine the feasibility, safety, and tolerability of oral Fecal Microbiota Transplantation (FMT) in adolescents (aged 13-17) with Attention-Deficit/Hyperactivity Disorder (ADHD).
Eligibility
Inclusion Criteria:
1. Between 13-17 years of age with consent of a legal guardian: Participants should be at least 13 years old and not older than 17 years at the day of screening (V1).
2. Have a primary diagnosis of ADHD as confirmed by the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID).
3. Be on a stable appropriate dose of an appropriate first-line pharmacological treatment for at least 8 weeks prior to the day of screening (V1).
a. First line pharmacotherapy treatment will be defined based on the CADDRA guidelines \[63\] and include the following
Amphetamine-based psychostimulants:
i. Mixed amphetamine salts (amphetamine and dextroamphetamine) ii. Lisdexamfetamine dimesylate
Methylphenidate-based psychostimulants:
i. Methylphenidate hydrochloride, Methylphenidate hydrochloride (extended release, multilayer release capsules) ii. Methylphenidate hydrochloride (extended release, OROS tablets) iii. Methylphenidate hydrochloride (controlled release, multi-layer beat capsules) iv. Methylphenidate hydrochloride (extended-release oral suspension)
4. Have a score of ≥ 18 on the inattention subset (questions 1-9) and/or the hyperactivity/impulsivity subset (questions 10-18) of the SNAP-IV 26-Item Parent Rating Scale on the day of screening (V1) and the baseline visit (V2).
5. Able to communicate and complete study assessments in English.
6. Able to comply with all protocol procedures.
7. Consenting guardian
Exclusion Criteria:
1. Participant meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Criteria for the following conditions according to the MINI-KID:
1. Diagnosis of a Substance Use Disorder within the last 3 months prior to screening. \*(Criteria should include Alcohol and Non-Alcohol substances except Cannabis)
2. Moderate or severe Substance Use Disorder for Cannabis use in the last 3 months
3. Currently active high suicidality. Eligibility of Participants who meet criteria for moderate suicidality is determined by clinical judgment of Principal Investigator.
4. Active Anorexia Nervosa or Bulimia Nervosa in the last 3 months.
5. Tic Disorders
6. Psychosis
7. Obsessive Compulsive Disorder
8. Bipolar Disorder
9. Conduct Disorder
2. Participant has a score of ≥ 8 on the oppositional defiant subset of the SNAP-IV 26-Item Parent Rating Scale (questions 19-26) on the day of screening (V1).
3. Intellectual or learning disability based on previous documented diagnosis or clinical judgment of Principal Investigator.
4. Documented diagnosis of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS).
5. Documented diagnosis of schizophrenia or schizoaffective disorder.
6. Documented diagnosis of Autism Spectrum Disorder (ASD) or currently undergoing assessment for suspected ASD.
7. Use of systemic antibiotics for medical purposes within the last 3 months prior to the day of screening (V1).
8. Use of prebiotics or probiotics for medical purposes for more than 2 weeks within the last 3 months prior to the day of screening (V1).
a) Eligibility and required washout period of participants with use of over-the-counter prebiotics or probiotics will be determined by clinical judgment of Principal Investigator.
9. Use of experimental drugs in the last 3 months prior to the day of screening (V1).
10. Documented clinical diagnosis of inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, and/or celiac disease.
11. Documented diagnosis of conditions causing immunosuppression and/or currently receiving immunosuppressive treatments.
12. Documented clinical diagnosis of significant bleeding disorders.
13. History of oropharyngeal dysphagia or other swallowing disorder, and/or self or study partner reported difficulty with taking oral capsules or pills.
14. Breastfeeding, pregnant or seeking to get pregnant during the course of this study. Female participants of childbearing age should be using an acceptable method of birth control (implants, injectable, combined oral contraceptives, IUDs, barrier contraceptives, sexual abstinence, or a vasectomized partner) for the duration of their participation in the trial.
15. Participants who are currently hospitalized or institutionalized.
16. Reported allergy to Vancomycin or Nitazoxanide
17. Hepatic dysfunction:
A) Documented history or current diagnosis of an acute or chronic hepatic disease (e.g., cirrhosis, hepatitis, hepatic impairment) OR
B) Abnormal - Liver Function Tests (LFTs): Screening laboratory results indicating clinically significant hepatic dysfunction:
* Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥3 the Upper Normal Limit (UNL)
* Total Bilirubin \> 1.5 × ULN (except in cases of documented Gilbert's Syndrome) 19. Renal dysfunction: A) Diagnosed Renal Disease: Any documented medical history or current diagnosis of kidney disease, acute kidney injury, or other clinically significant renal impairment. OR B) Abnormal Renal Function Tests: Screening laboratory results indicating significant renal dysfunction. Creatinine \> 1.5 × ULN\*
* Potential participants presenting with mild, non-clinically significant laboratory abnormalities (e.g., AST/ALT between 1.0 and 3.0 × ULN, or isolated borderline creatinine variations confirmation of enrollment into the study will be dependent of the study physician.
Primary outcome measure(s)
- Feasibility: Number of Participants Enrolled — 0-24 Weeks
Feasibility of FMT in an Adolescent Population With ADHD will be determined by: Successful enrollment of at least 45 participants across the four trial arms
- Feasibility: Number of Participants Completing Study Protocol — 0-24 weeks
Feasibility of FMT in an Adolescent Population With ADHD will be determined by: A minimum of 45 participants to complete study until the 24-week primary endpoint
- Feasibility: Number of Prescribed Capsule Doses Successfully Ingested — 0-24 weeks
Feasibility of FMT in an Adolescent Population With ADHD will be determined by adherence to study protocols: Receive at least 10/20 capsules per dosing visit
- Feasibility: Number of Participants Completing Required Study Visits — 0-24 weeks
Feasibility of FMT in an Adolescent Population With ADHD will be determined by the adherence to study protocols: Attend all visits - attend the baseline visit (Visit 2- V2) and at least 2 follow up visits (V4-10).
- Feasibility: Number of Participants Providing Required Biological Samples — 0-24 Weeks
Feasibility of FMT in an Adolescent Population With ADHD will be determined by the adherence to study protocols: Provide biological samples at baseline visit (V2) and at least 2 follow up visits (V4-10)
- Safety: Number of Participants With Treatment-Emergent Adverse Events — 0-24 weeks
Safety of FMT in an Adolescent Population With ADHD will be determined by:
Evaluating solicited and unsolicited adverse events, including serious adverse events
- Safety: Change From Baseline in Suicidality Score on the Columbia-Suicide Severity Rating Scale (C-SSRS) — 0-24 weeks
Safety of FMT in an Adolescent Population With ADHD will be determined by: Monitoring suicidality using the Columbia Suicide Severity Rating Scale (C-SSRS). The suicidal ideation subscale ranges from 0 (no ideation) to 5 (active suicidal ideation with specific plan and intent), and the suicidal behavior subscale ranges from 0 (no behavior) to 5 (completed suicide). Higher scores indicate greater severity of suicidality.
- Tolerability: Change From Baseline in Pittsburgh Side Effects Rating Scale (PSERS) Total Score — 0-24 weeks
Tolerability of FMT in Adolescents With ADHD will be determined by: Evaluating stimulant side effects using the Pittsburgh Side Effects Rating Scale (PSERS). Total scores range from 0 to 45 (or average score per item ranging from 0 to 3 across 15 symptoms: 0 = absent, 1 = mild, 2 = moderate, 3 = severe). Higher scores indicate greater severity of side effects.
- Tolerability: Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Total Score — 0-24 weeks
Tolerability of FMT in Adolescents With ADHD will be determined by: Evaluating gastrointestinal symptoms following colonic preparation and capsule dosing using the Gastrointestinal Symptom Rating Scale (GSRS). The GSRS is a 15-item questionnaire assessing GI symptoms across 5 domains (abdominal pain, reflux, indigestion, diarrhea, and constipation). Individual items are rated on a 7-point Likert scale ranging from 1 (no discomfort) to 7 (very severe discomfort), with total scores ranging from 15 to 105. Higher scores indicate greater GI symptom severity.
Trial sites (1)
| Facility | City | Region | Status |
|---|
| University of Calgary |
Calgary |
Alberta |
|
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