Investigating the Anti-inflammatory Effects of Frondanol in Adults With Inflammatory Bowel Disease

NCT05194007 | Completed Phase 2

• 1 other identifier: 1
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This is a pilot, prospective, double-blinded, two-arm, randomized controlled trial of the efficacy of Frondanol in comparison to placebo in decreasing bowel inflammation in patients with a clinical diagnosis of inflammatory bowel disease who are in remission and on standard of care treatment.

Conditions

Ulcerative Colitis Chronic Mild; Ulcerative Colitis Chronic Moderate; Crohn Colitis

Keywords

inflammatory bowel disease; Crohn disease; ulcerative colitis; frondanol; randomized controlled trial; placebo-controlled; chronic bowel inflammation

Outcome Measures

Primary Outcomes (8)

• To assess the change in plasma levels of cytokines between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment

  Cytokines will be measured in plasma samples.

  Baseline and after 6 months

• To assess the change in plasma levels of marker of inflammation between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment

  Marker of inflammation will be measured in plasma samples.

  Baseline and after 6 months

• To assess the change in biopsy mRNA levels between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment

  The mRNA levels of transcription factors involved in inflammation will be measured in tissue biopsy samples

  Baseline and after 6 months

• To assess the change in the biopsy mRNA levels between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment

  The mRNA levels of cytokines involved in inflammation will be measured in tissue biopsy samples

  Baseline and after 6 months

• To assess the change in the biopsy mRNA levels between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment

  The mRNA levels of markers involved in inflammation will be measured in tissue biopsy samples

  Baseline and after 6 months

• To assess the change in the proteins expression between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment

  The proteins expression of transcription factors involved in inflammation will be measured in tissue biopsy samples

  Baseline and after 6 months

• To assess the change in the proteins expression between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment

  The proteins expression cytokines involved in inflammation will be measured in tissue biopsy samples

  Baseline and after 6 months

• To assess the change in the proteins expression between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment

  The proteins expression of markers involved in inflammation will be measured in tissue biopsy samples

  Baseline and after 6 months

Secondary Outcomes (6)

• To assess the change in routine clinical parameters between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment:

  Baseline and after 2 months and after 4 months and after 6 months

• To assess the change in routine clinical parameters between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment:

  Baseline and after 2 months and after 4 months and after 6 months

• To assess the change in routine clinical parameters between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment:

  Baseline and after 2 months and after 4 months and after 6 months

• To assess the change in routine clinical parameters between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment:

  Baseline and after 2 months and after 4 months and after 6 months

• To assess the change in routine clinical parameters between IBD patients treated with Frondanol and those treated with placebo at baseline and after six months of treatment:

  Baseline and after 2 months and after 4 months and after 6 months

Study Arms (2)

Experimental -Frondanol

EXPERIMENTAL

Eligible participants will receive Frondanol capsule orally (1000 mg capsule twice daily) for 6 months

Drug: Frondanol

Placebo

PLACEBO COMPARATOR

Eligible participants will receive placebo capsule (twice daily) for 6 months

Drug: Placebo

Interventions

Frondanol DRUG

Frondanol capsule (1000 mg) will be administered orally (Twice daily) in the double blind settings

Experimental -Frondanol

Placebo DRUG

Placebo (corn starch) capsule will be administered orally (Twice daily) in the double blind settings

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A confirmed clinical diagnosis of IBD of any duration, age 18 years or older, with mild to moderate disease and on standard therapy.
• The diagnostic criteria for IBD include the presence of chronic diarrhea for more than four weeks, and evidence of active inflammation on endoscopy and chronic changes on biopsy.
• Patients with stable mild to moderate IBD will be eligible for the study.
• Stable IBD is defined as having stable symptoms over a period of several weeks, diagnostic evaluation has been completed and the patient has been on consistent medication.
• Mild to moderate IBD is indicated by a Partial Mayo score (Mayo Clinic Score/Disease Activity Index for Colitis) of between 1-6, and a total of Mayo score of 1-10.
• For patients with Crohn's disease, only those with Crohn's colitis will be included (patients with small bowel disease are eligible to enter the trial as long as they also have large bowel inflammation).

You may not qualify if:

• Pregnancy, breastfeeding, allergy to seafood or marine products
• Severe medical illness such as uncontrolled diabetes (HbA1C\>10), significant or unstable cardiovascular or pulmonary disease, impaired renal function (Cr\>2.0mg/dL), current or recent (\<1 year) malignancy, or other significant medical illness that in the view of the investigators may impair participation in the study.
• Patients with severe IBD (defined by a Partial Mayo score of 7-9 and a total Mayo score of 11-12, with active symptoms) will not be eligible to participate in the study.

Sponsors & Collaborators

• Mohammed Bin Rashid University of Medicine and Health Sciences: lead
• Mediclinic Middle East: collaborator
• Rashid Hospital: collaborator
• Dubai Health Authority: collaborator

Study Sites (2)

Mediclinic City Hospital

Dubai, United Arab Emirates

Location

Mediclinic Parkview Hospital

Dubai, United Arab Emirates

Location

Related Publications (14)

• Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573-621. doi: 10.1146/annurev-immunol-030409-101225.

  PMID: 20192811 BACKGROUND

• Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012 Jan;142(1):46-54.e42; quiz e30. doi: 10.1053/j.gastro.2011.10.001. Epub 2011 Oct 14.

  PMID: 22001864 BACKGROUND

• Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, Panaccione R, Ghosh S, Wu JCY, Chan FKL, Sung JJY, Kaplan GG. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017 Dec 23;390(10114):2769-2778. doi: 10.1016/S0140-6736(17)32448-0. Epub 2017 Oct 16.

  PMID: 29050646 BACKGROUND

• Friedrich M, Pohin M, Powrie F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity. 2019 Apr 16;50(4):992-1006. doi: 10.1016/j.immuni.2019.03.017.

  PMID: 30995511 BACKGROUND

• Kuhn KA, Schulz HM, Regner EH, Severs EL, Hendrickson JD, Mehta G, Whitney AK, Ir D, Ohri N, Robertson CE, Frank DN, Campbell EL, Colgan SP. Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity. Mucosal Immunol. 2018 Mar;11(2):357-368. doi: 10.1038/mi.2017.55. Epub 2017 Aug 16.

  PMID: 28812548 BACKGROUND

• Lee JS, Tato CM, Joyce-Shaikh B, Gulen MF, Cayatte C, Chen Y, Blumenschein WM, Judo M, Ayanoglu G, McClanahan TK, Li X, Cua DJ. Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability. Immunity. 2015 Oct 20;43(4):727-38. doi: 10.1016/j.immuni.2015.09.003. Epub 2015 Sep 29.

  PMID: 26431948 BACKGROUND

• Sairenji T, Collins KL, Evans DV. An Update on Inflammatory Bowel Disease. Prim Care. 2017 Dec;44(4):673-692. doi: 10.1016/j.pop.2017.07.010. Epub 2017 Oct 5.

  PMID: 29132528 BACKGROUND

• Ben-Horin S, Chowers Y. Tailoring anti-TNF therapy in IBD: drug levels and disease activity. Nat Rev Gastroenterol Hepatol. 2014 Apr;11(4):243-55. doi: 10.1038/nrgastro.2013.253. Epub 2014 Jan 7.

  PMID: 24393836 BACKGROUND

• Guerra I, Bermejo F. Management of inflammatory bowel disease in poor responders to infliximab. Clin Exp Gastroenterol. 2014 Sep 18;7:359-67. doi: 10.2147/CEG.S45297. eCollection 2014.

  PMID: 25258548 BACKGROUND

• Kelly MS. Echinoderms: their culture and bioactive compounds. Prog Mol Subcell Biol. 2005;39:139-65.

  PMID: 17152697 BACKGROUND

• Janakiram NB, Mohammed A, Bryant T, Lightfoot S, Collin PD, Steele VE, Rao CV. Improved innate immune responses by Frondanol A5, a sea cucumber extract, prevent intestinal tumorigenesis. Cancer Prev Res (Phila). 2015 Apr;8(4):327-37. doi: 10.1158/1940-6207.CAPR-14-0380. Epub 2015 Feb 5.

  PMID: 25657017 BACKGROUND

• Janakiram NB, Mohammed A, Zhang Y, Choi CI, Woodward C, Collin P, Steele VE, Rao CV. Chemopreventive effects of Frondanol A5, a Cucumaria frondosa extract, against rat colon carcinogenesis and inhibition of human colon cancer cell growth. Cancer Prev Res (Phila). 2010 Jan;3(1):82-91. doi: 10.1158/1940-6207.CAPR-09-0112.

  PMID: 20051375 BACKGROUND

• Subramanya SB, Chandran S, Almarzooqi S, Raj V, Al Zahmi AS, Al Katheeri RA, Al Zadjali SA, Collin PD, Adrian TE. Frondanol, a Nutraceutical Extract from Cucumaria frondosa, Attenuates Colonic Inflammation in a DSS-Induced Colitis Model in Mice. Mar Drugs. 2018 Apr 30;16(5):148. doi: 10.3390/md16050148.

  PMID: 29710854 BACKGROUND

• Ghelani H, Adrian TE, Ho SB, Akhras J, Azar AJ, Jan RK. Study protocol for a pilot randomized, double-blind, placebo-controlled trial to investigate the anti-inflammatory effects of Frondanol in adults with inflammatory bowel disease. Contemp Clin Trials Commun. 2022 Dec 1;31:101046. doi: 10.1016/j.conctc.2022.101046. eCollection 2023 Feb.

  PMID: 36544548 DERIVED

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases; Colitis, Ulcerative

Interventions

Frondanol-A5P

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All patients and investigators, excluding the study coordinator, will be blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This is a parallel group, randomized, double-blind, placebo-controlled pilot trial where participants will be randomized to receive either Frondanol 1000mg twice daily or placebo twice daily for 6 months.

Study Record Dates

• First Submitted: November 18, 2021
• First Posted: January 18, 2022
• Study Start: February 19, 2022
• Primary Completion: November 19, 2024
• Study Completion: November 19, 2024
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

AE (2)