Oral Administration of MB-102 Versus Dual Sugar Testing for Gut Permeability

Study Overview
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Brief Summary
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The objectives of the study are to evaluate the safety and tolerability of oral administration of MB-102, and to evaluate the use of MB-102 as a means of measuring gut permeability in normal participants (n=10) and in those with radiologic evidence of small bowel Crohn's disease (n=10).

Detailed Description
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This study is a single center, randomized, open label, cross-over study evaluating MB-102 versus dual sugar testing using lactulose and rhamnose for the assessment of gut permeability. Participants will be screened within 30 days of Day 1, and eligible participants will be randomized to receive either an oral dose of MB-102 or the dual sugar test on Day 1. At a second study visit occurring between 3 to 7 days after completion of the first test, participants will return to the study center for the second test. Following completion of the second test, participants will return to the study center 7 ±3 days for a follow-up visit to evaluate safety.

Official Title
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A Randomized Unblinded Feasibility Study Evaluating the Use of Oral Administration of MB-102 Versus Dual Sugar Testing for Gut Permeability in Normal Subjects and Subjects With Active Small Bowel Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: Lactulose/Rhamnose solution
* Drug: MB-102


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for all participants: Age > 18 years - male or non-pregnant or lactating females Participants willing to comply with study requirements Participants who have signed an informed consent form Normal or non-clinically significant screening and baseline 12 lead electrocardiogram (ECG) in the opinion of the principal investigator (PI) Estimated glomerulofiltration rate (eGFR) > 75 mL/min/1.73 m^2 Agreement to not utilize nonsteroidal anti-inflammatory drugs (NSAIDs) until study completion. Inclusion criteria for participants with Crohn's disease: Participants with active small bowel Crohn's disease diagnosed by an abnormal Magnetic Resonance Enterography (MRE) within 1 month prior to screening Active Crohn's disease must be characterized by mucosal hyperemia, and/or bowel wall thickening and/or vascular engorgement Exclusion criteria for all participants: Women who are pregnant, lactating, or planning to become pregnant during the study, or women who are of childbearing potential unwilling to use an adequate method of birth control a. Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 7 days post dose Participation in another interventional trial within 30 days of dosing or concurrently enrolled in any other medical research study which could impact the results of the study Unable to tolerate an overnight fast NSAID use within 14 days of Day 1 History of drug or alcohol abuse within the past year Diagnosis of ulcerative colitis, indeterminate colitis, pseudomembranous colitis, or celiac disease Prior or current diagnosis of an autoimmune disease Gastrointestinal surgery (including appendectomy) within 12 weeks prior to screening or has surgery planned or deemed likely to require surgery during the study Type 1 or 2 diabetes History of severe allergic hypersensitivity reactions (unacceptable adverse events) or anaphylactoid reaction to any allergen including drugs, or MB-102 (intolerance to a drug is not considered a drug allergy) Known history of testing positive for acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) Site personnel immediately associated with the study or their immediate family members Any characteristics which, in the opinion of the investigator, makes the participant a poor candidate for participation in the clinical trial Prior exposure to MB-102 Any changes to chronic medication therapy or initiation of new medications between Testing Day 1 and Testing Day 2 Current urinary tract infection Body mass index > 30 kg/m^2 Prior history of small bowel malignancy or resection surgery Unable to meet the requirements of the study including 12+ hour study visits Additional exclusion criteria for normal participants: Fecal transplant within 1 year Prior or current graft-vs.-host disease Prior or current history of diverticulitis Current or prior history of fatty liver Current use of any biologic therapy or current use of the following medications: sulfasalazine, mesalamine, olsalazine, balsalazide, prednisone, cyclosporine, azathioprine, 6-mercaptopurine, tacrolimus, methotrexate, intravenous immunoglobulin, anti-diarrheal agents Prior antibiotic therapy within 30 days of screening Undiagnosed chronic gastrointestinal upset or food intolerance history Recent history of significant unplanned weight loss, blood in the stool or acute episodes of diarrhea First-degree relative (sibling, parent, child) has inflammatory bowel disease (Crohn's disease, ulcerative colitis, proctitis, indeterminate colitis) History of Crohn's disease Additional exclusion criterion for participants with Crohn's disease: - Participant on Total Parenteral Nutrition (TPN)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lactulose/Rhamnose<br>1000 mg of lactulose and 200 mg of rhamnose administered orally as a 10 mL solution | Drug: Lactulose/Rhamnose solution<br>* Lactulose/Rhamnose solution administered orally followed by measurement of excreted lactulose and rhamnose in urine<br>|
| Experimental: MB-102<br>4 μmol of MB-102/kg body weight administered orally as a solution | Drug: MB-102<br>* MB-102 solution administered orally followed by measurement of excreted MB-102 in urine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean urine concentration of MB-102 over time in normal participants and in those with Crohn's disease | Urine samples will be collected pre-dose (time 0), each time the participant voids, and at the protocol-defined time points after oral administration of MB-102. The total volume of urine excreted will be recorded. Urine samples will be analyzed using validated analytical methods. | Pre-dose and 1, 2, 4, 6, 8, 10, and 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between MB-102 excretion and the results of dual sugar testing in normal participants and in those with Crohn's disease | For MB-102 excretion evaluation, urine samples will be collected pre-dose (time 0), each time the participant voids, and at the protocol-defined time points after oral administration of MB-102. The total volume of urine excreted will be recorded. Urine samples will be analyzed using validated analytical methods. For the dual sugar test, participants will consume a 10 mL solution (1000 mg of lactulose and 200 mg of rhamnose). Urine will be collected pre-dose (time 0), each time the participant voids, and at the protocol-defined time points after consuming the sugar solution. The total volume of urine excreted will be recorded. Urine samples will be analyzed using validated analytical methods. | Pre-dose and 1, 2, 4, 6, 8, 10, and 12 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MB-102, Gut permeability, Intestinal permeability