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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to assist children with Short Bowel Syndrome (SBS). SBS hinders nutrient absorption, often requiring children to depend on intravenous (IV) nutrition, which can lead to serious complications. The trial explores a treatment called RELiZORB, a small device that aids in digesting fats in tube feedings, potentially reducing the need for IV nutrition. Children with SBS who require IV nutrition for more than half of their daily intake might be suitable candidates for this trial.

As an unphased trial, this study provides a unique opportunity for children to potentially benefit from an innovative treatment approach.

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 prior data suggests that this device is safe for children with malabsorption syndrome?

Research has shown that RELiZORB is safe and generally well-tolerated. Studies have demonstrated that it helps patients absorb fats better by breaking them down before they enter the body, particularly benefiting those with conditions like cystic fibrosis.

One study found no major side effects, indicating that RELiZORB is generally safe to use. Designed to work with feeding tubes, it is ideal for individuals who have trouble digesting fats. Overall, RELiZORB appears to improve nutrition without causing significant issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

RELiZORB is unique because it is designed to enhance the digestion of fats directly within the feeding tube system, which is particularly beneficial for individuals with malabsorption syndrome. Unlike standard care options that often rely on enzyme pills or dietary modifications, RELiZORB uses an innovative cartridge that breaks down fats into absorbable fatty acids and monoglycerides before they enter the body. This method not only simplifies the process for individuals who rely on tube feeding but also aims to reduce dependency on parenteral nutrition, which is a more invasive and complex treatment. Researchers are excited about RELiZORB because it offers a more efficient and potentially more comfortable way to manage malabsorption, improving nutritional uptake directly at the source.

What evidence suggests that RELiZORB is effective for malabsorption syndrome?

Research has shown that RELiZORB, the treatment under study in this trial, helps people with digestion problems absorb fats more effectively. Studies found that RELiZORB use increases the amount of fatty acids in the blood, which are crucial for growth and energy. Patients using RELiZORB also reported fewer stomach issues, such as diarrhea, over time. Specifically, there was a noticeable improvement in growth, with steady increases in height and weight over a year. This suggests that RELiZORB is important for children with conditions that hinder fat absorption. ^{1 2 3 6 7}

Who Is on the Research Team?

Mark Puder, MD, PhD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2950456225000016

Development of a registry to evaluate immobilized lipase ... This prospective direct-to-patient observational registry collects real-world data regarding medical history, growth, quality of life, and progression towards ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6155360/

Absorption and Safety With Sustained Use of RELiZORB ... RELiZORB use was found to be safe, well tolerated, and resulted in increased levels of FAs in RBCs and plasma.

3. relizorbhcp.com relizorbhcp.com/study-results/

Proven to Hydrolyze Fats and Improve Fat Absorption 1 No reported incidences of diarrhea at Day 90 · Overall, the number of participants reporting GI symptoms decreased from Day 30 to 90 · No participants ...

4. alcresta.com alcresta.com/news/alcresta-therapeutics-announces-enrollment-of-first-patient-in-clinical-trial-evaluating-use-of-relizorb-in-critical-care-patients-at-inova-fairfax-medical-campus/

Alcresta Therapeutics Announces Enrollment of First ... Studies have demonstrated that RELiZORB is safe, well tolerated, and effective in improving fat absorption for patients with pancreatic ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1097%2FMPG.0000000000002984

Evaluation of the Effectiveness of In‐line Immobilized ... Following use of immobilized lipase cartridge out to 12 months, patients experienced significantly steady increase in height and weight and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02750501

Absorption and Safety With Sustained Use of RELiZORB ... Protocol 0000498: Multicenter, open label study to evaluate the effect of sustained RELiZORB (immobilized lipase) cartridge use during enteral feeding on fat ...

7. alcresta.com alcresta.com/clinical/

Clinical Studies Results from this study demonstrated that RELiZORB, when used per the intended use, was safe and well-tolerated and reduced signs of gastrointestinal ...