Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Connecticut Children's Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Connecticut Children's Medical Center
ClinicalTrials.gov Identifier:
NCT01536535
First received: February 16, 2012
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

This is a multi-center, open-label study to determine the safety and effectiveness (how well it works) of two standardized treatments called "mesalamine" (Pentasa®) and "prednisone" in children with newly diagnosed UC. Standardized treatments are types of treatments agreed upon and used by many qualified doctors. The medications being used in this study are considered "standard of care". Currently the ways in which these medicines are used (doses, frequency of dosing) may vary from site to site. This study will determine response to a standardized way of giving these medicines.

This study will also identify biomarkers for ulcerative colitis. Biomarkers are things that doctors can find in blood, stool, or bowel tissue that indicate how much inflammation there is in the bowel, how the inflammation is produced, and whether the inflammation is responding to treatment. Collecting response and remission (free of symptoms) information on these standardized treatments and the "biomarkers" can possibly help doctors create a model, or plan to know which children with UC may respond quickly, or which children may develop complications.


Condition Intervention Phase
Ulcerative Colitis
Drug: Mesalamine
Drug: Prednisone
Drug: Corticosteroids followed by mesalamine (Pentasa)
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Open-label Study Evaluating the Safety and Efficacy of Standardized Initial Therapy Using Either Mesalamine or Corticosteroids Then Mesalamine to Treat Children and Adolescents With Newly Diagnosed Ulcerative Colitis.

Resource links provided by NLM:


Further study details as provided by Connecticut Children's Medical Center:

Primary Outcome Measures:
  • Corticosteroid free remission (SFR) [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    Relative to other patients, those who have a PUCAI<10 at 4 weeks from start of therapy will be more likely to be in corticosteroid free remission (PUCAI<10) at 52 weeks while receiving the aminosalicylate mesalamine only as maintenance therapy without the need for rescue therapy with IM, CI, anti-TNFα, or surgery.


Secondary Outcome Measures:
  • Corticosteroid free remission [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

    The secondary endpoints are defined relative to start of therapy:

    • PUCAI <10 at 4 weeks
    • SFR at 12 weeks without the need for rescue therapy
    • SFR at 26 weeks without the need for rescue therapy
    • SFR at 104 weeks without the need for rescue therapy
    • Endoscopic response (Mayo score reduced by ≥1) and being 0,1 at week 52
    • Endoscopic remission (Mayo score 0) at week 52
    • IMPACT - III at 52 and 104 weeks
    • Colectomy free status during the follow-up period


Estimated Enrollment: 430
Study Start Date: June 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mesalamine Only

mesalamine (Pentasa®) comes in 500mg capsules, and doses will need to be rounded to the nearest 500mg increment, with a maximum dose of 76 mg/kg/day. The average dose for the pediatric population will be approximately 70 mg/kg/day. Patients will be allowed to escalate to the final dose over 4 days to minimize sideeffects such as headache.

If a patient does not respond to mesalamine then prednisone will be added to the treatment.

Drug: Mesalamine
Pentasa comes in 500mg capsules, and doses will need to be rounded to the nearest 500mg increment, with a maximum dose of 76 mg/kg/day. The average dose for the pediatric population will be approximately 70 mg/kg/day. Patients will be allowed to escalate to the final dose over 4 days to minimize side-effects such as headache.
Other Name: Pentasa
Experimental: Corticosteroids/mesalamine
Patients will begin with Corticosteroids, which will be weaned as tolerated and mesalamine added.
Drug: Prednisone
Initiate treatment with prednisone, 1-1.5 mg/kg/day, (maximum 40-60 mg in a single morning dose, either as tablet or liquid equivalent), rounded up to the nearest 5 mg value. This dose will be continued for 2 weeks to assess response.
Drug: Corticosteroids followed by mesalamine (Pentasa)
500 mg capsules 70-75 mg/kg per day
Other Name: Pentasa to be used after 2 weeks of prednisone

Detailed Description:

Ulcerative Colitis (UC) denotes a phenotype of chronic inflammatory bowel disease (IBD), where inflammation is localized to the colonic mucosa, and extends from the rectum proximally in varying extents. The disorder is thought to result from an inappropriate activation of the mucosal immune system by antigens derived from both the host epithelium and the enteric flora, in genetically susceptible individuals. UC is strikingly heterogeneous with respect to age of onset, anatomical extent and disease course, with some experiencing chronically active severe disease, while others have intermittent periods of clinical remission and disease exacerbation. Patients' therapeutic responses vary. The reasons underlying such variability are not well understood. Although it has been widely hypothesized that several genes may influence the development of UC, and modify its phenotypic expression and severity, to date there are few confirmed examples of such relationships.

It has been postulated that the 5-aminosalicylate drugs exert their anti-inflammatory effect locally at the intestinal mucosa. Mechanisms likely include inhibition of 5-lipoxygenase resulting in decreased production of leukotriene B4, scavenging of reactive oxygen metabolites, prevention of up-regulation of leukocyte adhesion molecules, and inhibition of IL-1 synthesis. Though multiple studies have shown the efficacy of aminosalicylates in inducing and maintaining remission in adults with UC, there are few data in children.

Corticosteroids have been the mainstay of treatment of severe UC since efficacy was first demonstrated in the 1955 randomized controlled trial by Truelove and Witts. Recent practice guidelines developed in adults support their use because of rapid onset of action and significant efficacy though CS dependency is noted. Though no controlled data on their use have been reported in children they are frequently used in this population. A recent report from investigators leading the prospective Pediatric IBD Collaborative Research Group Registry described 97 subjects with a diagnosis of UC and a minimum of 1 year follow-up; 79% received CS. At diagnosis 81% of CS treated patients had moderate/severe disease, and 81% had pancolitis. Clinically inactive disease, determined by physician global assessment, was noted in 60% at 3 months following CS therapy, but by one year 45% were considered CS dependent despite the frequent use of IM. Among those children with initially moderate to severe disease in clinical remission at 3 months, about two-thirds had stopped the CS by one year.

  Eligibility

Ages Eligible for Study:   4 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 4years and ≤17 years at initiation of therapy (achieved 4th birthday, not yet 18th)
  • Weight ≥15 kg
  • New diagnosis of ulcerative colitis established by standard clinical, endoscopic, and histologic features at the PROTECT study site
  • Colitis extending beyond the rectosigmoid (Paris classification E2, E3, or E4)[144]. If a patient is seriously ill and the clinician does not advance the colonoscope beyond the sigmoid colon but the clinical condition of the patient highly suggests more extensive disease then that patient is eligible for study.
  • Disease activity by PUCAI of ≥10 at diagnosis
  • No therapy previously initiated to treat the newly diagnosed ulcerative colitis
  • Stool culture negative for routine enteric pathogens (Salmonella, Shigella, Campylobacter, E. coli 0157:H7) and Clostridium difficile toxin. Recent successful treatment for Clostridium difficile does not exclude a patient if toxin now absent. However, the patient must be a minimum of 5 weeks from the time treatment was started at the time toxin is absent.
  • Stool study negative for enteric parasites (ova and parasites)
  • Parent/guardian consent and patient assent
  • Ability to remain in follow-up for a minimum of one year from diagnosis
  • Female patients of child bearing age must have a negative urine pregnancy test and practice acceptable contraception (e.g., abstinence, intramuscular or hormonal contraception, two barrier methods (e.g., condom, diaphragm, or spermicide), intrauterine device, verbal report of the partner with history of vasectomy, or be surgically sterile). All female patients of childbearing potential (post-menarche) will undergo urine pregnancy testing at screening and must not be lactating.

Exclusion Criteria:

  • Clinical, endoscopic, radiologic, or histologic evidence suggesting CD consistent with Paris and NASPGHAN criteria[144, 145]
  • A previous diagnosis of inflammatory bowel disease for which treatment was given
  • Evidence of any active enteric infection at the time of study entryUse of any oral CS for non-gastrointestinal indication within the past 4 weeks (e.g., asthma). Use of inhaled CS does not exclude a patient.
  • History of use of IM or anti-TNFα agent for other medical conditions (e.g., juvenile rheumatoid arthritis) within the past 6 months
  • Use of Accutane within the past 4 weeks
  • Use of any investigational drug within the past four weeks
  • Use of any 5-aminosalicylate within the past 4 weeks
  • Pregnancy
  • Subjects with poorly controlled medical conditions (e.g. diabetes, congestive heart failure)
  • Proctitis or proctosigmoiditis only (Paris classification E1) on colonoscopic evaluation
  • Chronic renal disease (BUN and serum creatinine >1.5 times the upper normal limit)
  • Hepatic disease (AST or ALP greater than 3 times the upper normal limit in the absence of concomitant liver disease associated with IBD following full evaluation)
  • History of allergy or hypersensitivity to salicylates, aminosalicylates, or any component of the Pentasa capsule.
  • History of coexisting chronic illness or evidence of significant organic or psychiatric disease on medical history or physical examination, which, in the Investigator's opinion, would prevent participation in the study
  • History or presence of any condition causing malabsorption or an effect on gastrointestinal (GI) motility, or history of extensive small bowel resection (greater than half the length of the small intestine).
  • The finding of Helicobacter pylori at the time of evaluation does not exclude the patient from the study. Whether to treat this patient for Helicobacter pylori and when will be left to the discretion of the site.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01536535

Contacts
Contact: Jeffrey Hyams, MD (860) 545-9532 jhyams@connecticutchildrens.org
Contact: Sonia Davis, DrPH (919) 966 - 8333 davissm@email.unc.edu

  Hide Study Locations
Locations
United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Lisette Macias    310-206-0688    Lmacias@mednet.ucla.edu   
Principal Investigator: David Ziring, MD         
University of California at San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Elizabeth Garnett    415-514-4423      
Contact: Alix Wilson    (415) 502-2425    alix.wilson@ucsf.edu   
Principal Investigator: Mel Heyman, MD         
United States, Connecticut
Connecticut Children's Medical Center Recruiting
Hartford, Connecticut, United States, 06106
Contact: Krista Spada       kspada@connecticutchildrens.org   
Contact: Jeffrey Hyams, MD    860-545-9532    jhyams@connecticutchildrens.org   
Principal Investigator: Jeffrey Hyams, MD         
United States, Florida
Nemours Children's Clinic Recruiting
Jacksonville, Florida, United States, 32207
Contact: Julie Castigliego    904-697-3920    jcastigl@nemours.org   
Principal Investigator: Jonathan Evans, MD         
United States, Georgia
Emory Children's Center Recruiting
Atlanta, Georgia, United States, 30322
Contact: Corinthian Bryant    404-727-4432    Corinthian.bryant@emory.edu   
Contact: Cathy Brashear    (404) 727-1190    cathy.brashear@emory.edu   
Principal Investigator: Cary Sauer, MD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago,, Illinois, United States, 60611-2605
Contact: Elizabeth Kirwan    312-227-4582    ekirwan@luriechildrens.org   
Contact: Kristin Johnson    (312) 227-4650    krjohnson@luriechildrens.org   
Principal Investigator: Jennifer Strople, MD         
United States, Indiana
Riley Children's Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Trisha Davis    317-948-5858    tawilson@iu.edu   
Contact: Gail Waltz    (317) 944-9656    gwaltz@iu.edu   
Principal Investigator: Marian Pfefferkorn, MD         
United States, Maryland
John Hopkins Children's Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Vivian Abadom    410-955-0779    vabadom1@jhmi.edu   
Principal Investigator: Maria Oliva-Hemker, MD         
United States, Massachusetts
Children's Hospital of Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Michael Butler    617-355-4370    Michael.Butler@childrens.harvard.edu   
Contact: Paul Rufo, MD, MMSc    (617) 355-2962    Paul.rufo@childrens.harvard.edu   
Principal Investigator: Paul Rufo, MD         
United States, Minnesota
University of Minnesota Medical Center Recruiting
Minneapolis, Minnesota, United States, 55454
Contact: Shannon Riggs    612-624-2422    riggs049@umn.edu   
Principal Investigator: Boris Sudel, MD         
United States, New Jersey
Goryeb Children's Hospital / Atlantic Health Recruiting
Morristown, New Jersey, United States, 07962
Contact: Annette Langseder    973-971-7747    annette.langseder@atlantichealth.org   
Contact: Katherine D'Addio    (973) 971-6517      
Principal Investigator: Joel Rosh, MD         
United States, New York
Women and Children's Hospital of Buffalo Recruiting
Buffalo, New York, United States, 14222
Contact: Christine Roach    716-878-7199      
Principal Investigator: Susan Baker, MD         
Cohen Children's Medical Center Recruiting
New Hyde Park, New York, United States, 11040
Contact: Kathy Grancher    718-470-3363      
Principal Investigator: James Markowitz, MD         
Mt Sinai Hospital Recruiting
New York, New York, United States, 10029
Contact: Rachael Schneider    212-241-4859    rachael.schneider@mssm.edu   
Contact: Clare Ceballos    (212) 241-7349    clare.ceballos@mountsinai.org   
Principal Investigator: Keith Benkov, MD         
Morgan Stanley Children's Hospital Recruiting
New York, New York, United States, 10032
Contact: Carmen Liriano    212-342-3552    crl58@cumc.columbia.edu   
Contact: Elena Reynosa       er2564@columbia.edu   
Sub-Investigator: Joel Lavine, MD         
Sub-Investigator: Neera Gupta, MD         
Golisano Children's Hospital SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
Contact: Karen Bilynsky    315-464-7209    bilynskk@upstate.edu   
Contact: Deb Carlson    (315) 464-7507    carlsodj@upstate.edu   
Principal Investigator: Prateek Wali, MD         
United States, North Carolina
University of North Carolina at Chapel HIll Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Jacquelyn Hores    919-966-7443    jacquelyn_hores@med.unc.edu   
Contact: Mary Lewis    (919) 843-9547    mary_lewis@med.unc.edu   
Principal Investigator: Michael Kappelman, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Ramona Bezold    513-636-1412      
Principal Investigator: Lee Denson, MD         
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Beth Skaggs    614-722-3487    Beth.Skaggs@nationwidechildrens.org   
Contact: Casey Cook    (614) 722-3024    Casey.cook@nationwidechildrens.org   
Principal Investigator: Brendan Boyle, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Maren Wennberg    215-590-1990    WennbergM@email.chop.edu   
Contact: Kelly Kachelries    (215) 590-0971    cochlinke@email.chop.edu   
Principal Investigator: Robert Baldassano, MD         
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Amy Bookser    412-692-8453    Amy.Bookser@chp.edu   
Contact: Erin Sandene       erin.sandene@chp.edu   
Principal Investigator: David Keljo, MD         
United States, Rhode Island
Hasbro Children's Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Barbara Bancroft    401-444-2884    bbancroft@lifespan.org   
Contact: Gina Ruggieri    (401) 444-2275    GRuggieri@lifespan.org   
Principal Investigator: Neal LeLeiko, MD         
United States, Tennessee
Monroe Carell Jr. Children's Hospital at Vanderbilt Recruiting
Nashville, Tennessee, United States, 37232
Contact: Cynthia Womack-Ramirez    615-322-4137    cynthia.h.womack-ramirez@vanderbilt.edu   
Principal Investigator: Dedrick Moulton, MD         
United States, Texas
UT Southwestern Recruiting
Dallas, Texas, United States, 75235
Contact: Deborah McElroy    214-456-8792      
Principal Investigator: Ashish Patel, MD         
United States, Utah
Primary Children's Medical Center (University of Utah) Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Ann Rutherford    801-585-9495    ann.rutherford@hsc.utah.edu   
Principal Investigator: Stephen Guthery, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Nicholas Peterson    414-266-4844    npeterso@mcw.edu   
Contact: Adriane Rozmarynowski    (414) 266-5721    Arozmarynows@mcw.edu   
Principal Investigator: Joshua Noe, MD         
Canada, Nova Scotia
IWK Health Centre Recruiting
Halifax, Nova Scotia, Canada, B3k6r8
Contact: Bradley MacIntyre    (902) 470-7009    brad.macintyre@iwk.nshealth.ca   
Contact: Amanda Hood    (902) 470-6595    Amanda.hood@iwk.nshealth.ca   
Principal Investigator: Anthony Otley, MD         
Canada, Ontario
Children's Hospital of Eastern Ontario Recruiting
Ottawa, Ontario, Canada, K1H8L1
Contact: Ruth Singleton    (613) 737-7600 ext 2516    rsingleton@cheo.on.ca   
Contact: Kristin Moran    (613) 737-7600 ext 4131    kmoran@cheo.on.ca   
Principal Investigator: David Mack, MD         
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Michelle Ouzounis    (416) 813-8665    michelle.ouzounis@sickkids.ca   
Principal Investigator: Anne Griffiths, MD         
Sponsors and Collaborators
Connecticut Children's Medical Center
Investigators
Principal Investigator: Jeffrey Hyams, MD Connecticut Children's Medical Center
Principal Investigator: Lee Denson, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Sonia Davis, DrPH Collaborative Studies Coordinating Center - UNC-CH
  More Information

Additional Information:
No publications provided

Responsible Party: Connecticut Children's Medical Center
ClinicalTrials.gov Identifier: NCT01536535     History of Changes
Other Study ID Numbers: U01-DK095745-01, 1U34DK090804
Study First Received: February 16, 2012
Last Updated: August 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Connecticut Children's Medical Center:
Ulcerative Colitis
mesalamine
corticosteroids
PROTECT

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes
Prednisone
Mesalamine
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 29, 2014