Efficacy of CROWN in Repair and Maintenance of the Intestinal Mucosa in Patients With CD Receiving Anti-TNF Therapy (PIONEER-CD)

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effectiveness of a Nutritional Intervention in Improving the Intestinal Mucosal Health Status in Subjects With Crohn's Disease (CD) Receiving Anti-TNF Therapy

The purpose of this study is to evaluate CROWN's efficacy in supporting the repair and maintenance of the intestinal mucosa of patients with moderately to severely active Crohn's Disease receiving anti-Tumor Necrosis Factor (TNF) therapy (infliximab, adalimumab, certolizumab)

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: CROWN; Drug: CROWN Placebo

Detailed Description

The purpose of this study is to evaluate the effectiveness of an orally administered nutritional intervention (CROWN) in subjects with Crohn's Disease (CD) to support Standard Of Care (SOC) treatment in the repair and maintenance of the intestinal mucosa over a 24 week period. SOC is defined as having been on a stable maintenance dose of an anti-Tumor Necrosis Factor (TNF) agent within 24 weeks of its initiation.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • CROWN Site 0032
    • Huntsville, Alabama, United States, 35801
      • CROWN Site 0011
  • Arkansas
    • Little Rock, Arkansas, United States, 72212
      • CROWN Site 0091
  • California
    • Los Angeles, California, United States, 90033
      • CROWN Site 0017
    • Rialto, California, United States, 92377
      • CROWN Site 0054
    • Ventura, California, United States, 93003
      • CROWN Site 0013
  • Colorado
    • Aurora, Colorado, United States, 80045
      • CROWN Site 0030
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • CROWN Site 0028
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • CROWN Site 0073
  • Florida
    • Naples, Florida, United States, 34102
      • CROWN Site 0096
  • Illinois
    • Chicago, Illinois, United States, 60611
      • CROWN Site 0081
    • Urbana, Illinois, United States, 61801
      • CROWN Site 0050
  • Kansas
    • Topeka, Kansas, United States, 66606
      • CROWN Site 0036
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • CROWN Site 0019
  • Louisiana
    • Bastrop, Louisiana, United States, 71220
      • CROWN Site 0002
    • Baton Rouge, Louisiana, United States, 70809
      • CROWN Site 0003
    • Shreveport, Louisiana, United States, 71105
      • CROWN Site 0029
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • CROWN Site 0051
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • CROWN Site 0014
    • Chesterfield, Michigan, United States, 48047
      • Crown Site 0006
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • CROWN Site 71
  • New York
    • Great Neck, New York, United States, 11021
      • CROWN Site 0020
    • Mineola, New York, United States, 11501
      • CROWN Site 0084
    • Poughkeepsie, New York, United States, 12601
      • CROWN Site 0039
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • CROWN Site 0012
    • Chapel Hill, North Carolina, United States, 27599
      • CROWN Site 0018
    • Raleigh, North Carolina, United States, 27612
      • CROWN Site 0034
    • Rocky Mount, North Carolina, United States, 27804
      • CROWN Site 0021
  • Oregon
    • Portland, Oregon, United States, 97210
      • CROWN Site 0093
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • CROWN Site 0033
    • Philadelphia, Pennsylvania, United States, 19140
      • CROWN Site 0040
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • CROWN Site 0094
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • CROWN Site 0041
  • Texas
    • Houston, Texas, United States, 77030
      • CROWN Site 0004
    • Houston, Texas, United States, 77030
      • CROWN Site 0086
  • Utah
    • Orem, Utah, United States, 84058
      • CROWN Site 0007
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • CROWN Site 0016
  • Washington
    • Bellevue, Washington, United States, 98004
      • CROWN Site 0098
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • CROWN Site 0009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Crohn's Disease patient who has derived clinical benefit from the Standard of Care therapy, but continues to have evidence of incomplete healing of the intestinal mucosa.

1. Adults (18-85 years of age) with a known history of symptomatic CD confirmed by endoscopy or radiology
2. CDAI score ≤ 350
3. Active endoscopic disease (SES-CD score ≥ 6) documented during the study screening phase or SES-CD score ≥ 4 if isolated ileal disease
4. On a stable dose of infliximab, adalimumab, or certolizumab therapy for 8 weeks prior to randomization as part of SOC
5. Able to consume oral nutrition for up to 24 weeks consisting of two 4 oz (120 ml) servings daily
6. Able to understand the informed consent process, willing to follow study instructions and likely to complete all required visits and procedures, including the use of an electronic device to collect study data, home computer or tablet and internet access to complete online food frequency questionnaire, and undergo 2 endoscopies in a 6 month period

Exclusion Criteria:

Subjects with one or more of the following criteria are excluded from participation in the study:

1. If female, subject is pregnant, nursing, or planning to become pregnant during the study period or is of childbearing potential and unable or unwilling to use a reliable form of contraception during the study
2. Fistula known to be contributing to diarrhea
3. Recent or current history of bowel obstruction
4. Stricturing disease with evidence of bowel dilation proximal to stricture on imaging
5. Anticipated need for gastrointestinal surgical therapy in the next 6 months
6. Current treatment with a systemic corticosteroid at dose greater than 20 mg of prednisone (or equivalent) at screening
7. Change in any antimetabolite therapy within 8 weeks prior to randomization
8. Current treatment with antibiotics for CD (ciprofloxacin, metronidazole) at screening
9. Current ostomy
10. Serious infection, neoplasia or other medical conditions which would interfere with participation in the study, in the opinion of the Investigator
11. Evidence of Clostridium difficile infection in the previous 4 weeks
12. History of non-compliance with clinical protocols
13. Active participation in another CD trial or received an investigational product within the past 4 weeks
14. Diagnosis of celiac disease
15. Known sensitivity to milk or soy protein
16. In the Investigator's opinion, subject has any condition or situation which makes the subject unsuitable for study participation, may put the subject at significant risk, or may confound the study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CROWN; CROWN: A nutritionally based therapy with a high protein content, formulated as a powder. Twice a day, preferable 1 hour before or more than 2 hours after meals, for up to 24 weeks	Drug: CROWN; A nutritionally based therapy, formulated as a powder, administered twice a day, preferable 1 hour before or more than 2 hours after meals, for up to 24 weeks
Placebo Comparator: CROWN Placebo; Placebo: An appearance and volume matched formulated powder. Twice a day, preferable 1 hour before or more than 2 hours after meals, for up to 24 weeks	Drug: CROWN Placebo; Placebo, formulated as a powder, administered twice a day, preferable 1 hour before or more than 2 hours after meals, for up to 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Simple Endoscopic Score - Crohn's Disease (SES-CD)	Measuring intestinal health improvement is the Week 24 change from baseline in Simple Endoscopic Score - Crohn's Disease (SES-CD)	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma amino acid level	Change from baseline in plasma amino acid levels	Week 12 and at Week 24
Quality of Life Score - Inflammatory Bowel Disease Questionnaire (IBDQ)	Change from baseline in quality of life score in IBDQ	Weeks 12 and 24
Quality of Life Score - Work Productivity Activity Index - Crohn's Disease(WPAI-CD)	Change from baseline in quality of life score in WPAI-CD	Weeks 12 and 24
Inflammatory biomarkers	Proportion of subjects with a normalization of inflammatory biomarkers (C-Reactive Protein (CRP) and fecal calprotectin)	Week 24
Endoscopic response	Proportion of subjects with endoscopic response based on SES-CD score, defined as a decrease in the SES-CD of at least 3 points from baseline, and no worsening of either component of the PRO2 (abdominal pain or liquid or soft stool frequency)	Week 24
Corticosteroid-free	Proportion of subjects who are corticosteroid-free	Week 12

Collaborators and Investigators

• Sponsor: Prometheus Laboratories
• Collaborators: Nestlé Health Science Spain; Nestec Ltd.
• Investigators: Study Chair: James Lewis, M.D., University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: June 1, 2016
• First Submitted That Met QC Criteria: June 3, 2016
• First Posted (Estimate): June 8, 2016

Study Record Updates

• Last Update Posted (Actual): June 28, 2019
• Last Update Submitted That Met QC Criteria: June 26, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Crohn's Disease; inflammatory bowel disease; mucosal healing; Nutritional intervention; Medical Food
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 13.06.CLI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No