RELiZORB for Malabsorption Syndrome

Overseen By Mark Puder, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Must be taking: Parenteral lipid

Must not be taking: Pancreatic enzymes, Teduglutide, Growth hormone, Cisapride

Disqualifiers: Chronic liver disease, Pancreatic insufficiency, Cystic fibrosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 90 days

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have used pancreatic enzymes, cisapride, or certain other medications within 30 days before screening.

What data supports the effectiveness of the treatment RELiZORB for Malabsorption Syndrome?

RELiZORB, an in-line digestive cartridge, has been shown to effectively break down over 90% of fats in enteral nutrition formulas, making them easier to absorb. This has been demonstrated in studies involving patients with conditions like short bowel syndrome and exocrine pancreatic insufficiency, where improved fat and vitamin absorption was observed. ^{1 2 3 4 5}

Is RELiZORB safe for use in humans?

RELiZORB has been evaluated for safety in a clinical trial for children with short bowel syndrome, and it is designed to help with fat digestion in patients receiving enteral nutrition. The treatment is generally considered safe, with studies showing it effectively breaks down fats in enteral nutrition without significant safety concerns. ^{1 2 3 5 6}

How is the treatment RELiZORB unique for malabsorption syndrome?

RELiZORB is unique because it is an immobilized lipase cartridge that helps break down fats in the digestive system, which is different from other treatments that may not directly aid in fat digestion. This makes it particularly useful for people with malabsorption syndrome who struggle to absorb fats from their diet. ^{7 8 9 10 11}

What is the purpose of this trial?

Children with inadequate intestinal absorption due to loss of large amounts of small bowel require intravenous nutrition (feeding through the vein) to sustain hydration and nutrition to avoid starvation and dehydration; however, intravenous (IV) nutrition can lead to complications including liver failure. Tube feeding directly to the small intestine avoids the complications of IV nutrition, but fats are not fully digestible due to inadequate bowel function. We propose to predigest the fat using a small cartridge attached to the feeding tube to allow for rapid absorption with the possibility of reducing or eliminating the need for intravenous nutrition

Research Team

Mark Puder, MD, PhD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for children aged 2-18 with Short Bowel Syndrome (SBS) who rely on intravenous nutrition but can tolerate some tube feeding. They should have a stable nutritional regimen, an existing feeding tube, and not have had any significant changes in their enteral nutrition or parenteral nutrition requirements recently. Kids with certain conditions like liver disease unrelated to SBS or recent use of specific medications are excluded.

Inclusion Criteria

I have short bowel syndrome and need parenteral nutrition or have a significantly shorter bowel.

My nutritional needs via IV have been stable for the last month.

I or my guardian understand the study's needs and can attend all visits.

Exclusion Criteria

I do not have an untreated blockage or narrowing in my intestines.

I do not have severe stomach or bowel movement disorders.

Your blood test shows high levels of triglycerides, over 400 mg/dL.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the RELiZORB enzyme cartridge with enteral nutrition daily for 90 days

90 days

Visits at days 7, 14, 28, 60, and 90

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• RELiZORB

Trial Overview The study tests RELiZORB, a cartridge that predigests fats in the feeding tube formula, potentially improving nutrient absorption and reducing the need for IV nutrition. The goal is to see if this device helps kids absorb more nutrients directly through their intestines over a period of 90 days.

Participant Groups

Group I: Relizorb treatment Experimental Treatment 1 Intervention

Patients will have tube feeds placed through chamber and evaluate wean from parenteral nutrition

RELiZORB is already approved in United States for the following indications:

Approved in United States as RELiZORB for:

• Fat malabsorption in pediatric patients (ages 2 and above) and adult patients receiving enteral nutrition

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Alcresta Therapeutics, Inc.

Industry Sponsor

Trials

6

Recruited

240+

Findings from Research

The study is evaluating the safety and efficacy of the RELiZORB enzyme cartridge in children aged 2-18 with short bowel syndrome (SBS) who are dependent on parenteral nutrition (PN), aiming to reduce PN dependence and improve fat absorption over a 90-day period.

Preclinical studies have shown that the RELiZORB cartridge can significantly enhance fat and fat-soluble vitamin absorption, which could help prevent complications associated with long-term PN use in SBS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fat digestion using RELiZORB in children with short bowel syndrome who are dependent on parenteral nutrition: Protocol for a 90-day, phase 3, open labeled study. Tsikis, ST., Fligor, SC., Mitchell, PD., et al.[2023]

RELiZORB is a novel in-line digestive cartridge that effectively addresses the need for pancreatic enzyme replacement therapy (PERT) in patients with exocrine pancreatic insufficiency (EPI) receiving enteral nutrition, demonstrating compatibility with various formulas.

In clinical evaluations, RELiZORB was able to hydrolyze over 90% of fats in enteral nutrition formulas into absorbable fatty acids and monoglycerides, significantly improving fat absorption for patients who struggle with traditional long-chain triglycerides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Options for addressing exocrine pancreatic insufficiency in patients receiving enteral nutrition supplementation. Freedman, SD.[2018]

In a study involving 15 male Yorkshire piglets with short bowel syndrome, the use of ALC-078 significantly improved the absorption of fat-soluble vitamins like vitamin D and E compared to untreated resected animals, indicating its potential efficacy in enhancing nutrient absorption.

ALC-078-treated piglets showed similar weight gain and fat absorption rates compared to those without intestinal resection, suggesting that it may help mitigate the effects of fat malabsorption in short bowel syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in-line digestive cartridge increases enteral fat and vitamin absorption in a porcine model of short bowel syndrome. Tsikis, ST., Fligor, SC., Secor, JD., et al.[2023]

An investigation of six pancreatin preparations from three companies revealed that all had lipase activity exceeding the amounts stated on their packaging, sometimes by more than double.

This significant variation in enzyme potency suggests that patients may need to rely on symptom relief to gauge their enzyme supplementation, highlighting the importance for clinicians to consider potential differences in lipase activity when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stated versus actual lipase activity in pancreatic enzyme supplements: implications for clinical use. O'Hare, MM., McMaster, C., Dodge, JA.[2019]

In a study of 23 adults with pancreatic insufficiency, pH-sensitive enteric-coated pancreatic lipase microspheres improved fat utilization to 76% compared to 63% with other enzyme supplements, indicating greater efficacy in nutrient absorption.

Over a year-long study with 22 patients, those using the microspheres gained an average of 4.0 kg and experienced a return to a near-normal lifestyle, highlighting both the safety and effectiveness of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of a pancreatic enzyme supplement. Valerio, D., Whyte, EH., Schlamm, HT., et al.[2017]

Pancreatic enzyme replacement therapy is a safe and effective treatment for nutrient malabsorption due to pancreatic insufficiency, significantly reducing symptoms like steatorrhea and fat malabsorption.

Current challenges in treatment include ensuring enzymes reach the duodenum without being destroyed in the stomach, and research is focused on developing new enzymes and delivery systems to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme replacement therapy for pancreatic insufficiency: present and future. Fieker, A., Philpott, J., Armand, M.[2022]

Cocrystallization of rebamipide with coformers like citric acid and oxalic acid significantly improved its solubility and bioavailability, achieving a 1.6-2.5 fold increase compared to pure rebamipide.

The new cocrystals not only enhanced the solubility and dissolution rate by 7-13 times but also showed improved anti-ulcer, anti-inflammatory, and antioxidant properties, indicating their potential as a more effective formulation for treating ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering a Remedy to Modulate and Optimize Biopharmaceutical Properties of Rebamipide by Synthesizing New Cocrystal: In Silico and Experimental Studies. Jindal, A., Singh, R., Tomar, S., et al.[2022]

Rabeprazole is a powerful proton pump inhibitor that provides rapid and sustained acid suppression, making it effective for treating conditions like gastroesophageal reflux disease and ulcers, with symptom relief starting from the first dose.

Due to its unique metabolism, rabeprazole has a lower risk of drug-drug interactions, enhancing its safety profile for patients who may be taking multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rabeprazole for the treatment of acid-related disorders. Marelli, S., Pace, F.[2013]

Rebamipide nanosuspensions (REB-NSs) were successfully created using a combination of acid-base neutralization and microfluidization, leading to a faster dissolution rate compared to conventional Mucosta(®) tablets.

The pharmacokinetic study showed that REB-NSs resulted in a slight increase in plasma drug concentration and improved gastrointestinal distribution, which may enhance the therapeutic effects of Rebamipide in protecting the GI mucosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A potent preparation method combining neutralization with microfluidization for rebamipide nanosuspensions and its in vivo evaluation. Shi, Y., Zou, M., An, Y., et al.[2016]

Lansoprazole significantly impacted the accuracy of the 14C-urea breath test (UBT) for detecting Helicobacter pylori, leading to equivocal or false negative results in 61% of patients, while high-dose ranitidine caused this issue in only 18%.

The effects on UBT accuracy were linked to the degree of gastric acid suppression, and both medications' impacts on test results resolved within 5 days after stopping the drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lansoprazole and ranitidine affect the accuracy of the 14C-urea breath test by a pH-dependent mechanism. Chey, WD., Woods, M., Scheiman, JM., et al.[2022]

In a study involving 248 healthy subjects, novel rabeprazole extended-release (ER) formulations provided significantly longer gastric acid suppression over 24 hours compared to esomeprazole and rabeprazole delayed-release (DR), with mean durations of 18.5-20.2 hours versus 15.9 hours and 15.2 hours, respectively.

The enhanced acid suppression with rabeprazole-ER was particularly notable during the night-time, with 57.0-72.4% of the night showing intragastric pH >4.0, compared to only 32.8% for esomeprazole and 34.0% for rabeprazole-DR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers. Morelli, G., Chen, H., Rossiter, G., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Fat digestion using RELiZORB in children with short bowel syndrome who are dependent on parenteral nutrition: Protocol for a 90-day, phase 3, open labeled study. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Options for addressing exocrine pancreatic insufficiency in patients receiving enteral nutrition supplementation. [2018]

3. England pubmed.ncbi.nlm.nih.gov

An in-line digestive cartridge increases enteral fat and vitamin absorption in a porcine model of short bowel syndrome. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Stated versus actual lipase activity in pancreatic enzyme supplements: implications for clinical use. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of a pancreatic enzyme supplement. [2017]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Enzyme replacement therapy for pancreatic insufficiency: present and future. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Engineering a Remedy to Modulate and Optimize Biopharmaceutical Properties of Rebamipide by Synthesizing New Cocrystal: In Silico and Experimental Studies. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Rabeprazole for the treatment of acid-related disorders. [2013]

9. England pubmed.ncbi.nlm.nih.gov

A potent preparation method combining neutralization with microfluidization for rebamipide nanosuspensions and its in vivo evaluation. [2016]

10. United States pubmed.ncbi.nlm.nih.gov

Lansoprazole and ranitidine affect the accuracy of the 14C-urea breath test by a pH-dependent mechanism. [2022]

11. England pubmed.ncbi.nlm.nih.gov

An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers. [2021]