Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, Trichuris Suis Ova, Inflammatory Bowel Disease, Mucus
Brief summary
The purpose of this study is to understand the immune response activated in the human gastrointestinal tract by Trichuris Suis Ova (TSO) in patients with ulcerative colitis.
Detailed description
The concept of helminthic therapy (using worms to treat diseases) is supported by experiments in mouse models as well as several clinical studies. TSO, which are purified eggs from the porcine whipworm Trichuris suis, are being investigated in clinical trials as a potential therapeutic agent for the treatment of active Crohn's disease, relapsing multiple sclerosis, peanut and tree nut allergy, and adults with autistic disorders. The goal of this study is to understand the immune mechanisms activated in the human gastrointestinal tract by treatment with TSO, which may lead to improvements in the symptoms of ulcerative colitis (UC). TSO have been shown to have a clinical benefit on a subset of patients with UC in a previous randomized placebo-controlled trial (Summers et al. 2005). However, the mechanisms of action of TSO on the intestinal mucosa remain unclear. We propose an exploratory 24-week mechanistic randomized double-blind placebo-controlled crossover study of TSO in patients with established and active UC to better characterize similarities and differences in the immune mechanisms of the intestinal mucosa in response to TSO. We hypothesize that treatment with TSO will lead to an anti-inflammatory immune response in some individuals with UC through an increase in intestinal mucus production and modulation of Th1, Th2, Th17, and T-regulatory effector lymphocyte populations.
Interventions
2,500 eggs by mouth every two weeks for 12 weeks
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 72 Years
Healthy volunteers
No
Inclusion criteria
* Subjects will be outpatients between the ages of 18 and 72. * Subjects must have a biopsy-proven diagnosis of ulcerative colitis for greater than three months. * There should be evidence of active disease with a total Mayo score of 6 to 10 points (scores range from 0 to 12, with higher scores indicating more severe disease activity). * There should be moderate (marked erythema, lack of vascular pattern, friability, erosions) to severe (spontaneous bleeding, ulceration) active disease on colonoscopy (Mayo endoscopic score of at least 2) at time of enrollment. * Laboratory inclusion criteria will require a hemoglobin level of \>9.0 g/dL, a white blood count between 5,000 and 15,000/μL, a platelet count of \>100,000μL, a blood urea nitrogen \< 40mg/dL, a serum creatinine of \<2.0mg/dL, a total bilirubin \< 2.5 mg/dL, and an alkaline phosphatase of \<250U/dL. * Women will be required to have a negative urine pregnancy test and to practice birth control. * The following medications will be allowed and continued throughout the study: Oral or rectal sulfasalazine, mesalamine, or mesalamine derivative (maintenance therapy of \> 8 weeks, stable dose of \> 4 weeks); Oral corticosteroid (prednisone, prednisolone, or budesonide) at an equivalent dose of a maximum of 40mg daily prednisone (maintenance therapy of \>4 weeks, stable dose of \> 2 weeks), azathioprine or 6-mercaptopurine (maintenance therapy of \> 8 weeks, stable dose of \> 4 weeks). * Subjects must have the ability to provide informed consent and be willing to keep all scheduled appointments for the duration for the study period.
Exclusion criteria
* Inpatients, pregnant patients, patients with impaired cognition, patients with a history of active substance abuse in the past six months, and children. * Patients with a history of bowel surgery in the prior six months or who currently or previously had an ileostomy or colostomy. * Patients with active malignancy or treatment with anticancer drugs in the past 5 years, have a history of colorectal cancer or dysplasia, or a history of neoplasm of the gastrointestinal tract. * Female patients who are pregnant, breastfeeding, wishing to become pregnant during study participation, or unwilling to use birth control. * Patients with white blood count \<5,000 or \>15,000/mm3; platelet count \<150,000 per μl; or iron or vitamin B12 deficiency. Correction of lab exclusion is allowed provided that medical condition is not deemed to put patient at risk and stability of result is sustained for a minimum of 30 days. * Patients with stools positive for enteric pathogens, ova, or parasites at Screening * Patients with active hepatitis B virus or hepatitis C virus infection or have been exposed to human immunodeficiency virus (HIV). * Patients who have received an anti-tumor necrosis factor inhibitor (e.g. infliximab) within 12 weeks prior to Screening * Patients who have received antibiotic, antifungal or antiparasitic medication in the last 2 weeks prior to Screening and/or would potentially require this during the study treatment period. * Patients with evidence of poor compliance with medical advice and instruction including diet or medication. * Patients who are unable or unwilling to swallow study medication suspension. * Patients will be excluded if they have previously attempted helminthic therapy. * There must not be evidence of fulminant colitis or a Mayo score of greater than 10 * Patients will be excluded if other clinically significant disease is present that could interfere with protocol compliance or interpretation of the results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline of Mucus Production at 12 Weeks and 24 Weeks as Assessed by Histopathology | Baseline, 12 weeks, 24 weeks |
| Change From Baseline of Effector Lymphocyte Populations (Th1, Th2, Th17, and T-regulatory Cells) at 12 and 24 Weeks as Assessed by Flow Cytometry of Peripheral Blood Mononuclear Cells and Isolated Leukocytes From Pinch Biopsies | Baseline, 12 weeks, 24 weeks |
| Change From Baseline of Bacterial Composition and Attachment at 12 Weeks and 24 Weeks as Assessed by Real-time Polymerase Chain Reaction and 454 Sequencing of Pinch Biopsies and Stool Specimens | Baseline, 12 weeks, 24 weeks |
| Change From Baseline of Gene Expression at 12 Weeks and 24 Weeks as Assessed by Microarray and Real-time Polymerase Chain Reaction Analysis of Pinch Biopsies | Baseline, 12 weeks, 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mayo Score From Baseline at 12 Weeks and 24 Weeks | Baseline, 12 weeks, 24 weeks | To assess ulcerative colitis disease activity |
| Change From Baseline of the Simple Clinical Colitis Activity Index at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 Weeks | Baseline, 2, 4, 6, 8, 10, 14, 16, 18, 20, 22 weeks | To assess ulcerative colitis disease activity without requiring endoscopy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trichuris Suis Ova Followed by Placebo Subjects in this arm will receive Trichuris suis ova for 12 weeks, followed by placebo for 12 weeks after crossover
Trichuris suis ova: 2,500 eggs by mouth every two weeks for 12 weeks | 2 |
| Placebo Followed by Trichuris Suis Ova Subjects in this arm will receive placebo for 12 weeks, followed by Trichuris suis ova for 12 weeks after crossover
Trichuris suis ova: 2,500 eggs by mouth every two weeks for 12 weeks | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Trichuris Suis Ova Followed by Placebo | Placebo Followed by Trichuris Suis Ova | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 |
Outcome results
Primary
Change From Baseline of Bacterial Composition and Attachment at 12 Weeks and 24 Weeks as Assessed by Real-time Polymerase Chain Reaction and 454 Sequencing of Pinch Biopsies and Stool Specimens
Time frame: Baseline, 12 weeks, 24 weeks
Population: Because of the small sample size of this study, investigators decided it was not possible to draw meaningful conclusions from the outcome measures and outcome measures were not collected or analyzed as originally planned. Therefore, no outcome measure data is available.
Primary
Change From Baseline of Effector Lymphocyte Populations (Th1, Th2, Th17, and T-regulatory Cells) at 12 and 24 Weeks as Assessed by Flow Cytometry of Peripheral Blood Mononuclear Cells and Isolated Leukocytes From Pinch Biopsies
Time frame: Baseline, 12 weeks, 24 weeks
Population: Because of the small sample size of this study, investigators decided it was not possible to draw meaningful conclusions from the outcome measures and outcome measures were not collected or analyzed as originally planned. Therefore, no outcome measure data is available.
Primary
Change From Baseline of Gene Expression at 12 Weeks and 24 Weeks as Assessed by Microarray and Real-time Polymerase Chain Reaction Analysis of Pinch Biopsies
Time frame: Baseline, 12 weeks, 24 weeks
Population: Because of the small sample size of this study, investigators decided it was not possible to draw meaningful conclusions from the outcome measures and outcome measures were not collected or analyzed as originally planned. Therefore, no outcome measure data is available.
Primary
Change From Baseline of Mucus Production at 12 Weeks and 24 Weeks as Assessed by Histopathology
Time frame: Baseline, 12 weeks, 24 weeks
Population: Because of the small sample size of this study, investigators decided it was not possible to draw meaningful conclusions from the outcome measures and outcome measures were not collected or analyzed as originally planned. Therefore, no outcome measure data is available.
Secondary
Change From Baseline of the Simple Clinical Colitis Activity Index at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 Weeks
To assess ulcerative colitis disease activity without requiring endoscopy
Time frame: Baseline, 2, 4, 6, 8, 10, 14, 16, 18, 20, 22 weeks
Population: Because of the small sample size of this study, investigators decided it was not possible to draw meaningful conclusions from the outcome measures and outcome measures were not collected or analyzed as originally planned. Therefore, no outcome measure data is available.
Secondary
Change in Mayo Score From Baseline at 12 Weeks and 24 Weeks
To assess ulcerative colitis disease activity
Time frame: Baseline, 12 weeks, 24 weeks
Population: Because of the small sample size of this study, investigators decided it was not possible to draw meaningful conclusions from the outcome measures and outcome measures were not collected or analyzed as originally planned. Therefore, no outcome measure data is available.