Microbiota Transfer Therapy Clinical Trial

Frequently Asked Questions

If you have additional questions please direct them to information@pitthopkins.org.

This will be a Phase 2 Trial to determine the safety, tolerability, and efficacy of Microbiota Transfer Therapy (MTT) for treating patients with Pitt Hopkins Syndrome and gastrointestinal disorders (chronic constipation and/or diarrhea).

Human gut microbiota play many roles in the body, including digestion of food, production of several vitamins, motility regulation, water regulation, and protection against pathogenic bacteria.  Thus, it is possible that FM will result in improvements if there are deficiencies in those areas.  

The researchers previously conducted a similar study for 18 children with autism, and found an 80% reduction in gastrointestinal symptoms, and a 25-45% reduction in autism-related symptoms (language, social interaction, behavior) – with most benefits continuing at two years after treatment stopped.

This will be a Phase 2 Trial to determine the safety, tolerability, and efficacy of Microbiota Transfer Therapy (MTT) for treating patients with Pitt Hopkins Syndrome and gastrointestinal disorders (chronic constipation and/or diarrhea).

There may be up to 20 participants enrolled but will begin with an initial 10 participants.

All clinical trials have guidelines about who can participate. The factors that allow someone to participate in a clinical trial are called “inclusion criteria” or “eligibility criteria” and those that disallow someone from participating are called “exclusion criteria.” These criteria are based on factors like age, gender, previous treatment history, and other medical conditions. Before joining a clinical trial, a participant must qualify, or be eligible to participate in the study.  See eligibility and exclusion criteria in other FAQs.  

Inclusion Criteria

1)    Children ages 7-17 years with Pitt Hopkins Syndrome (verified by genetic testing)

2)    GI disorder that has lasted for at least 2 years.

3)   No changes in medications, supplements, diet, or therapies in last 2 months, and no intention to change them during the Parts 1 and 2 of the clinical trial.

4)    Ability to swallow pills (without chewing)

5)    Review of last two years of medical records by the study physician. 

 

Participants must be registered in the CORDs Pitt Hopkins registry.   If you have not done so already, please register at the following link:   https://pitthopkins.org/research/how-to-get-involved-in-research-today/family-registry/

Exclusion Criteria

1) Antibiotics in last 3 months

2) Probiotics in last 2 months, or fecal transplant in last 12 months

3) Tube feeding

4) Severe gastrointestinal problems that require immediate treatment (life-threatening)

5) Ulcerative Colitis, Crohn’s Disease, diagnosed Celiac Disease, Eosinophilic Gastroenteritis, or similar conditions

6) Unstable, poor health (based on study physician’s opinion)

7) Recent or scheduled surgeries

8) Current participation in other clinical trials

9)     Allergy or intolerance to vancomycin or magnesium citrate

10) Clinically significant abnormalities at baseline on two blood safety tests:  Comprehensive Metabolic Panel, and Complete Blood Count with Differential. Note that some abnormalities may occur due to PTHS, so only those likely to significantly increase risk in this study would be grounds for exclusion, at the discretion of the study physician.

Children ages 7-17 years with Pitt Hopkins Syndrome (verified by genetic testing) are eligible for this trial.  

At this time, per FDA regulations, the trial is only open to residents of the United States.

Participants can apply at http://autism.asu.edu/content/pitt-hopkins-study.

Participants must also be registered in the CORDs Pitt Hopkins registry.   If you have not done so already, please register at the following link: https://pitthopkins.org/research/how-to-get-involved-in-research-today/family-registry/

Applications will be processed by the research team at ASU in the order they are received.

Given the Covid-19 situation, it will likely be conducted via telemedicine. 

Medications will be provided at no charge. Shipment costs will be covered.  We ask that families use their insurance company to cover a required basic physical exam and blood draw with their local primary care doctor, but if this is not covered the PHRF will pay for this. 

Travel stipends are available from the PHRF upon request. Please contact us at information@pitthopkins.org.

Enrollment for this clinical trial begins in October 2019.  Participants will need to travel to Arizona in approximately April 2020 to begin their participation in the clinical trial.   

No compensation will be provided for participation in the study.

If you do not reside in Arizona, Out-of-state participants will have the option of having subsequent blood draws and physical examinations done by their local physician, with a report being sent to the lead study physician.  The lead study physician will also talk to participants via Skype or similar video-conferencing as part of the physical examination process, and to conduct evaluations.

The vancomycin, magnesium citrate, and FM will be prescribed by the study physician after reviewing their baseline lab safety tests (CBC and metabolic panel). 

The vancomycin and FM will be refrigerated (both at ASU and at the participant’s homes), and transported under refrigerated conditions.

FM is light brown-colored powder in a capsule taken orally.  

 

Part 1:  Placebo-Controlled Treatment (14 weeks)

The trial will begin with a randomized, double-blind, placebo-controlled trial which will include a 10-day treatment with oral vancomycin (or placebo), then 1 day of magnesium citrate to cleanse the bowel of vancomycin and bacteria/feces (all participants, since its bowel-emptying effect cannot be blinded), followed by oral administration of FM (or placebo).  An initial high dose of FM (or placebo) for two days will be followed by a lower maintenance dose of FM (or placebo) for 12 weeks. 

Group A:  real treatment

Group B:  placebo vancomycin, real magnesium citrate, placebo FM

 

Part 2 Open-Label Observation and Cross-Over (14 weeks)

Group 1:  Observation over the next 14 weeks (no additional treatment)

Group 2:   They will receive the same treatment that group A received in part 1.  This includes 10 days of vancomycin, magnesium citrate, an initial high dose of FM for 2 days, and then a lower dose of FM for 12 weeks.

 

Part 3:  Follow-up

There will be a follow-up evaluation at 14 weeks after the end of part 2, to assess long-term efficacy and possible adverse effects.

FM is minimally manipulated, total fecal microbiota  derived from the stool of healthy donors. Donors are carefully screened via health status questionnaires, physical examinations, reviews of comprehensive medical history, clinical laboratory evaluations, serologic and genomic tests for infectious diseases and metabolic health, and stool-related pathogen tests.  The material from the donors is purified to remove the majority of non-bacterial material, washed, lyophilized, and encapsulated.

Stool donations from US healthy volunteers who are screened and tracked in the University of Minnesota stool collection program are processed into a FM-lyophilized product at Molecular and Cellular Therapeutics Center at the University of Minnesota (http://www.ahc.umn.edu/mct/).

There can be risks and side effects with the medicines used in the trial.  You should talk with your child’s doctor if you are considering this clinical trial.  In addition, you should talk to the researchers about the potential risks associated with MTT and the other medicines used in this trial.  

The possible benefits of your child’s (ward’s) participation in the research are a possible reduction of your child’s gastrointestinal problems.

Informed consent is the process of learning the key facts about a clinical trial before deciding whether or not to participate. This process is important to ensure that potential participant families understand the study’s purpose, potential benefits, and risks in participating as well as their other possible options.

Participation will take approximately 14-28 weeks, and 1-2 brief follow-ups at 14-28 weeks post-treatment. Participants will be randomly assigned to the treatment or placebo group, but after Part 1 of the study the placebo group will be switched to the actual treatment.

 

MTT involves a 10-day course of vancomycin (an antibiotic designed to kill harmful bacteria), a bowel cleanse with magnesium citrate, and then capsules containing microbiota from healthy, carefully screened human donors.  The Food and Drug Administration (FDA) has approved this investigational study of MTT for the possible treatment of gastrointestinal disorders in children with Pitt Hopkins Syndrome (PTHS).

 

The study design includes three parts:

 

Part 1:  Randomized, Placebo-Controlled Treatment (14 weeks)

Group A:  vancomycin, magnesium citrate, microbiota capsules

Group B:  placebo vancomycin, real magnesium citrate, placebo capsules

 

Part 2: Open-Label Observation and Cross-Over (14 weeks)

Group 1:  Observation over the next 14 weeks (no additional treatment)

Group 2:   vancomycin, magnesium citrate, microbiota capsules

 

Part 3:  Follow-up

There will be a follow-up evaluation at 14 weeks after the end of part 2, to assess long-term efficacy and possible adverse effects.

Clinical trials are carefully designed research studies in which people help doctors find ways to improve health and care related to specific diseases or medical conditions. Each study tries to answer scientific questions and to find better ways to treat that condition.  

A double–blind study is one in which neither the participants nor the experimenters know who is receiving a particular treatment. This procedure is utilized to prevent bias in research results. Double–blind studies are particularly useful for preventing bias due to demand characteristics or the placebo effect.

A placebo can be made to resemble an active medication or therapy so that it functions as a control; this is to prevent the recipient(s) or others from knowing (with their consent) whether a treatment is active or inactive, as expectations about efficacy can influence results.

Sponsor and Investigator:  James B. Adams, Ph.D.

         Arizona State University

         PO Box 876106

         Tempe, AZ 85287-6106 

Prof. Adams is the director of the Autism/Asperger’s Research Program at Arizona State University, which focuses on medical causes of autism, how to treat it, and how to prevent it.  He has published over 150 papers in peer-reviewed journals, including over 40 on autism-related research. He has led several clinical trials for ASD and assisted with several others.  He led the Phase 1 study on MTT, and is currently leading a study on “Microbiota Transfer Therapy (MTT) for Treating Gastrointestinal Problems in Adults with ASD.”

  

Co-Investigator:  Rosa Krajmalnik-Brown, Ph.D.

Biodesign Institute at Arizona State University

P.O. Box 875701

Tempe, AZ 85287-5701

Prof. Krajmalnik-Brown is a Professor in the School of Sustainable Engineering and the Built Environment, and in the Swette Center for Environmental Biotechnology in the Biodesign Institute at Arizona State University. She has extensive expertise in microbial ecology with more than 60 papers in peer-reviewed journals. She has led many studies determining the gut microflora structure and function.  She has worked with Prof. Adams on 4 previous autism microbiome studies, including the Phase 1 study on MTT for children with ASD and a current study on MTT for adults with ASD. 

  

Lead Physician:  Sharon McDonough-Means, MD

316 South Convent Ave

Tucson, AZ 85701

Dr. McDonough-Means is a fellowship-trained developmental pediatrician with a private practice in Tucson, Arizona.  She has been principal investigator on one NIH study, collaborated with University of Arizona and more recently ASU faculty on research studies, including several in Autistic Disorder with Prof. James Adams, including serving as the physician for the Phase 1 study of MTT for children with ASD.

  

 

You can contact the study coordinators with any questions:

Pompa Bhattacharjee: Pompa.Bhattacharjee@asu.edu
Carlos Robles: Carlos.Robles1@asu.edu

Glossary: 

FMT – Fecal Microbiota Transplant 

FM – Fecal Microbiota 

MTT – Microbiota Transfer Therapy

PHRF – Pitt Hopkins Research Foundation

PTHS – Pitt Hopkins Syndrome 

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