Fecal Transplant for Pediatric Patients Who Have Recurrent C-diff Infection

Visit 1 - screening visit: This visit will take about 1 hour. The study doctor will talk to
the patient about C-diff infection and fecal transplant in detail. Investigators will ask you
questions about your medical history and health. A complete physical examination will be
done. Investigators will order a pregnancy test (for girls who are old enough to become
pregnant) and take blood (about 1.5 teaspoons) to make sure you do not have any other illness
or infections (other than C-diff.) If the pregnancy test comes back positive on a patient who
is younger than age 18, both the patient and parent(s) will be informed. The study doctor
will then choose a possible stool donor. The study doctor will ask the donor to fill out a
questionnaire about their medical history, past and present diseases, allergies and
medications. If this donor seems suitable, blood and stool tests will be performed on the
donor.

Before the next visit: Before the fecal transplant is scheduled the study doctor will look at
your all of the lab results from you and the donor to make sure it is safe for the fecal
transplant to take place. This will take up to two weeks. If the donor is not a suitable
donor, another donor will be chosen. Every possible donor will need to sign a consent form
and fill out questionnaires. When a suitable donor is found, we will to schedule the fecal
transplant.

There are two ways in which the fecal transplant can be given. One is by enema and the other
is during a colonoscopy. The study doctor believes that the best way to give the transplant
is during a colonoscopy. If you needs to have a colonoscopy done for clinical purposes (in
the routine medical care of your C-diff infection), the fecal transplant will happen during
that procedure. The doctor will explain the colonoscopy to you in detail and will be given
special instructions on how to prepare for the colonoscopy. You will need to sign a separate
consent for the colonoscopy. The other way the fecal transplant can be given is by enema. If
you are not having a colonoscopy or for some other reason the doctor believes it is better to
do so, you will receive the transplant through an enema.

The study doctor will talk with you about stopping medicines that are not allowed during the
study. If you are taking antibiotics (such as metronidazole, vancomycin, or rifaximin,
nitazoxanide, and fidaxomicin) as a treatment for C-diff, you will be asked to stop these
medicines 2 days before the transplant.

Visit 2 - the day of the fecal transplant: This visit will take about 4-6 hours. A pregnancy
test will be repeated. If the pregnancy test comes back positive for a patient who is younger
than age, both the patient and parent will be informed. The study doctor will ask you and the
donor how they are feeling. If either the patient or the donor is not feeling well, the
transplant will be reschedule to another day. If both are well, the fecal transplant will
proceed.

On the morning of the transplant the donor will be asked to have a bowel movement in a
plastic container. The donor will bring this stool sample to the hospital to be processed.
This stool sample will be blended into a liquid.

The FMT can be given by either a colonoscopy or enema. The doctor will talk to you about
which method will be best for you.

Transplant by colonoscopy: Before the colonoscopy, the study doctor will ask questions about
your symptoms and medications. During the colonoscopy, the doctor will squirt one cupful (250
ml) of liquid into the colon using a special colonoscopy tube. The liquid will be made of
saline (salt water) and donor stool. The recovery time from the colonoscopy will be the same.

Transplant by enema: The study doctor will ask you questions about your symptoms and
medications. The patient's pants and underwear will be removed. A thin slippery tube will be
put into the patient's bottom (rectum). The tube will be pushed in as deep as we can without
pushing the tube hard. About 1 cupful of liquid will be gently squeezed into the rectum. The
liquid will be made of saline (salt water) and donor stool. We will ask the patient to lie
down on their left side for 30 minutes and keep the solution in for at least 45 minutes. The
patient will then be sent home.

After the transplant: The patient will be called at days 1, 7, 14 and months 1 and 6 to see
how they are feeling. The investigator's staff will ask some questions over the phone. The
phone call will take about 10 minutes. The patient may also call the study doctor anytime
with questions or concerns.

If belly pain or diarrhea continues one month after the transplant, the study doctor will
want to repeat a stool test for C-diff. Sometimes the patient is not cured and a second
transplant is needed. If a second transplant is needed, the same donor can be used if he/she
is willing. The second transplant will be done by enema. The donor would have lab (blood and
stool tests) done again to be sure she/he does not have any new infections or illness.

The donor may need to have the lab work done again if the transplant does not happen as
scheduled (cancellation, no-show or illness). HIV testing is one of the things we do on
potential donors. The HIV testing must be done no more than 14 days before the transplant.
The other required lab tests need to be done no more than 30 days before the transplant. The
date the transplant is rescheduled to will determine whether or not these tests need to be
done again.

Inclusion Criteria:

Recipient inclusion criteria:

- Documented laboratory-confirmed clostridium difficile infection

- Documentation of ongoing diarrhea at time of recruitment

- Children ≥2 years old, <18 years old; young adults >18 years old, <21 years old

- Undergoing clinically-indicated colonoscopy

- Recurrent c-diff infection (three or more occurrences)

Donor inclusion criteria:

- First-degree relative recommended, but not compulsory

- ≥ 18 years old

- In good health

- No antibiotic use within the last 90 days

- In "low risk" category on modified DHQ (See above)

Exclusion Criteria:

- Recipient exclusion criteria

- Severe comorbid condition (at discretion of the principal investigator)

- On immunosuppressive medications (high dose steroids 30 mg/kg of methylprednisolone)

- Severe or fulminant C. difficile colitis

- Toxic appearance

- Signs of hemodynamic instability

- Peritoneal signs on physical exam

- Anemia on complete blood count

- electrolyte imbalances on basic metabolic panel

- Considerations for Increased Risk of Adverse Events Should Be Given to patients with
decompensated liver cirrhosis, advanced HIV/acquired immune deficiency syndrome,
recent bone marrow transplant, or other cause of severe immunodeficiency.

- History of severe anaphylactic shock

Donor exclusion criteria:

- Abnormal stools

- Abdominal complaints

- History of inflammatory bowel disease or gastrointestinal malignancy

- Symptoms indicative of irritable bowel syndrome or other chronic pain syndromes (e.g.
chronic fatigue syndrome, fibromyalgia)

- History of systemic autoimmunity (e.g. multiple sclerosis, connective tissue disease)

- Recent use of potent immunosuppressive medications (calcineurin inhibitors, exogenous
glucocorticoids, biological agents, etc..)

- Recent ingestion of a potential allergen (e.g. nuts) where recipient has a known
allergy to this (these) agent(s)

- Known communicable disease

- Neurologic, neurodevelopmental or neurodegenerative disorders

- History of malignancy

- Has consumed any foods/medications to which the recipient is allergic within the
designated period of time