Chyme Reinfusion Device for Intestinal Failure

(REINFUSE Trial)

Not currently recruiting at 16 trial locations

Overseen By Caroline Alsweiler

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Insides Company

Disqualifiers: Bowel obstruction, Infections, Motility disorders, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new system designed to assist individuals with certain types of intestinal failure by reinfusing nutrients and fluids lost through enterocutaneous fistulas (abnormal connections between the intestine and the skin). The trial includes two groups: one receives standard care, while the other uses the Insides System, a chyme reinfusion device. This system suits individuals who rely on parenteral nutrition (receiving nutrients intravenously) and have specific visible openings on the abdomen from past surgeries. The study aims to improve nutrient absorption and fluid management in these patients. As an unphased trial, it provides a unique opportunity to contribute to innovative research that could enhance future treatment options.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does list several medical conditions and devices that would exclude you from participating, so it's best to discuss your specific situation with the trial coordinators.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the Chyme Reinfusion Device is safe for intestinal failure?

Research has shown that the Insides System is generally safe for people with intestinal failure. One study found it effective for managing type 2 intestinal failure, although patients require a short training period to use it. These studies identified no major safety issues. The treatment involves returning chyme (a mix of partly digested food and stomach fluids) to the intestine, which helps prevent nutrient and fluid loss. Patients who underwent this procedure tolerated it well. While the results are promising, potential participants should understand how the device works and discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for intestinal failure, which typically involves nutritional support through intravenous feeding, the Insides System offers a novel approach by reinfusing chyme directly into the intestines. This method could enhance nutrient absorption and improve gut health in patients with Type II intestinal failure who are dependent on parenteral nutrition. Researchers are excited about this treatment because it utilizes a unique delivery method that could reduce the reliance on intravenous feeding, potentially improving patients' quality of life and decreasing the risk of complications associated with long-term parenteral nutrition.

What evidence suggests that the Insides System is effective for intestinal failure?

Studies have shown that the Insides System, which returns partly digested food to the intestine, can help manage type 2 intestinal failure. In this trial, participants in the active treatment arm will receive chyme reinfusion using the Insides System. Research indicates that this system can improve nutrient absorption in the intestine and reduce the need for intravenous feeding. Patients using this system have started eating by mouth again and relied less on intravenous feeding in as little as three days. Additionally, the system may prevent dehydration and kidney problems while also shortening hospital stays. These findings suggest that the Insides System could be a promising option for those dealing with nutrient and fluid loss from enterocutaneous fistulas. ^{2 4 6 7 8}

Who Is on the Research Team?

Dermot Burke, MD

Principal Investigator

St. James Hospital, Leeds, UK

Are You a Good Fit for This Trial?

This trial is for adults over 21 with Type 2 Intestinal Failure who rely on parenteral nutrition due to enterocutaneous fistulas. They must have visible intestinal openings and be able to insert a feeding tube into the distal limb. Excluded are those with upcoming surgery, certain infections, systemic infection signs, pregnant or breastfeeding women, recent clinical study participants, specific bowel issues like obstruction or motility disorders, severe kidney disease, liver cirrhosis, coagulopathy, metal stents near the device area or active implantable devices.

Inclusion Criteria

A feeding tube can be placed in my digestive system opening.

I have visible surgical connections on my abdomen.

It has been at least 2 weeks since my dialysis access surgery.

Exclusion Criteria

You have active implantable medical devices, like devices that help with nerve stimulation or heart function.

I am currently infected with C. difficile.

I have liver cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chyme reinfusion using the Insides System for subjects with Type II intestinal failure dependent on PN

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Extension

Participants may continue to be monitored for long-term outcomes and device performance

Up to 60 days

What Are the Treatments Tested in This Trial?

Interventions

• The Insides System

Trial Overview The trial tests 'The Insides System,' a prosthetic designed to return nutrients and fluids from an intestinal fistula back into the intestine. It aims to reduce dependency on parenteral nutrition by reinfusing chyme (digestive fluid) through afferent and efferent limbs of the intestine in patients with this condition.

How Is the Trial Designed?

Group I: Active Experimental Treatment 1 Intervention

Reinfusion of chyme using the Insides System for subjects with Type II intestinal failure dependent on PN

Group II: Control Active Control 1 Intervention

Standard of care therapies in accordance with ASPEN and ESPEN treatment guidelines

The Insides System is already approved in European Union, United Kingdom for the following indications:

Approved in European Union as The Insides System for:

• Type 2 intestinal failure
• Enterocutaneous fistulas
• High-output enterostomies

Approved in United Kingdom as The Insides System for:

• Acute severe intestinal failure (type 2)
• High-output enterostomies
• Enterocutaneous fistulas

Who Is Running the Clinical Trial?

The Insides Company

Lead Sponsor

Trials

1

Recruited

40+

Green Lane Coordinating Centre Limited

Collaborator

BioValeo

Industry Sponsor

Databean

Industry Sponsor

Trials

6

Recruited

780+

The Insides Company Ltd. Manufacturer

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

Chyme reinfusion (CR) using the novel Insides System™ device successfully provided adequate nutritional support for a 66-year-old woman with a high-output enterocutaneous fistula, allowing her to stop parenteral nutrition (PN).

The device was easy for the patient to use with minimal nursing assistance, and side effects were manageable through patient-controlled adjustments, highlighting CR as a promising, cost-effective alternative for nutritional management in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chyme reinfusion nutritional management for enterocutaneous fistula: first international application of a novel pump technique. Solis, E., Wright, DB., O'Grady, G., et al.[2021]

The injectable reverse thermal gel (RTG) functionalized with carbon nanotubes (CNTs) supports long-term survival and improved function of cardiomyocytes (CMs), making it a promising alternative to traditional invasive implantation methods.

Compared to standard two-dimensional gelatin controls and a 3D RTG system without CNTs, the RTG-CNT system enhances CMs alignment, proliferation, and overall function, indicating its potential for effective cardiac tissue engineering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injectable Carbon Nanotube-Functionalized Reverse Thermal Gel Promotes Cardiomyocytes Survival and Maturation. Peña, B., Bosi, S., Aguado, BA., et al.[2023]

Chyme reinfusion (CR) significantly improved nutritional status in patients with Type 2 intestinal failure, leading to a 3.5% weight gain and a 5.4 g/L increase in plasma albumin, while also reducing the need for intravenous supplementation by 89%.

The study, which included 306 patients treated with CR over 18 years, demonstrated that CR effectively restored intestinal function, evidenced by a decrease in intestinal losses and improved absorption of nutrients, with no reported serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chyme Reinfusion in Intestinal Failure Related to Temporary Double Enterostomies and Enteroatmospheric Fistulas. Picot, D., Layec, S., Seynhaeve, E., et al.[2021]

The development of human intestinal microphysiological systems, like the 'Gut-on-a-Chip', allows for a more accurate simulation of human intestinal functions and diseases by incorporating key components such as gut microbiota and peristalsis-like motions.

These advanced models can help predict how the human intestine responds to drugs and therapies, making them valuable for testing the efficacy and safety of new treatments in a preclinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Farewell to Animal Testing: Innovations on Human Intestinal Microphysiological Systems. Kang, TH., Kim, HJ.[2020]

Pediatric heart failure, while rare, has a high mortality rate, but the young heart shows significant regenerative potential due to a higher number of cardiac progenitor cells, which could be harnessed for therapy.

Case reports and cohort studies suggest that autologous stem cell therapies, such as bone marrow mononuclear cells, have led to short-term improvements in heart function and clinical stability in critically ill children with severe heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical cardiac regenerative studies in children. Pavo, IJ., Michel-Behnke, I.[2020]

Long-term success of stem cell therapy for heart repair is limited by the modest retention of transplanted cells, which primarily stimulate the body's own repair mechanisms rather than becoming heart tissue themselves.

Improving the retention and survival of these transplanted cells is crucial for enhancing their effectiveness in restoring heart function, suggesting that new strategies are needed to address the challenges of cardiac engraftment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular mechanisms underlying cardiac engraftment of stem cells. Kanda, P., Davis, DR.[2018]

The Mini Gut (MiGut) platform is a scalable in vitro model that effectively mimics human colon physiology, allowing for extensive study of the gut microbiome and its interactions without the limitations of traditional animal models.

In a 9-week benchmarking study, MiGut demonstrated excellent repeatability and consistency with established gut models, enabling researchers to run multiple experiments simultaneously and generate clinically relevant data on microbiome interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MiGut: A scalable in vitro platform for simulating the human gut microbiome-Development, validation and simulation of antibiotic-induced dysbiosis. Davis Birch, WA., Moura, IB., Ewin, DJ., et al.[2023]

Adult cardiac stem cells (CSCs) exist in the heart and have limited ability to proliferate and differentiate in response to injury, which poses challenges for effective cardiac repair.

Transplanting CSCs expanded outside the body may require a combination of growth factors and tissue engineering to enhance their survival and function in the heart, while reprogrammed fibroblasts could serve as a promising alternative source for generating patient-specific stem cells for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stemming heart failure with cardiac- or reprogrammed-stem cells. Tateishi, K., Takehara, N., Matsubara, H., et al.[2021]

Short bowel syndrome (SBS) is a major cause of intestinal failure in neonates, leading to reliance on long-term parenteral nutrition, which can result in severe complications like sepsis and liver disease.

Neonatal piglet models are emerging as valuable tools for studying SBS due to their physiological similarities to human infants, allowing researchers to explore the disease's heterogeneity and develop new therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Piglet Models of Neonatal Short Bowel Syndrome. Lim, DW., Turner, JM., Wales, PW.[2015]

A new chyme reinfusion device was tested in ten patients and was found to be safe, with no serious device-related adverse events, while effectively allowing for the reinfusion of lost intestinal fluid.

The device showed clinical benefits such as enabling patients to resume oral diets, reducing the need for parenteral nutrition in four out of five patients, and aiding in electrolyte correction and hospital discharge for six out of ten patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chyme reinfusion device for gastrointestinal fistulas and stomas: feasibility study. Sharma, P., Davidson, R., Davidson, J., et al.[2021]

Chyme reinfusion (CR) is a promising and safe intervention for managing high-output double enterostomies (DES) and enteroatmospheric fistulas (EAF), with no serious adverse events reported in 481 cases reviewed.

Benefits of CR include weight gain, reduced need for parenteral nutrition, and improved liver function, although the methods used for effluent collection and reinfusion need to be more efficient and user-friendly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chyme Reinfusion for Small Bowel Double Enterostomies and Enteroatmospheric Fistulas in Adult Patients: A Systematic Review. Bhat, S., Sharma, P., Cameron, NR., et al.[2020]

Automated chyme reinfusion (CR) in patients with intestinal failure significantly restored the bile salt-FGF19 signaling pathway, which is crucial for regulating bile salt synthesis and improving gut-liver function.

After 21 days of CR, patients showed improved nutritional status and normalized liver tests, indicating that CR not only enhances intestinal function but also protects against liver injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chyme Reinfusion Restores the Regulatory Bile Salt-FGF19 Axis in Patients With Intestinal Failure. Koelfat, KVK., Picot, D., Chang, X., et al.[2022]

The NEC-on-a-Chip model effectively mimics the key features of necrotizing enterocolitis (NEC) in premature infants, including inflammation and gut barrier disruption, using intestinal enteroids and infant-derived microbiota.

This innovative model allows for detailed study of NEC pathophysiology and supports the development of personalized medicine approaches for testing new treatments, utilizing valuable clinical samples from infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip. Lanik, WE., Luke, CJ., Nolan, LS., et al.[2023]

Human intestinal organoids (HIOs) created from human pluripotent stem cells can successfully engraft in vivo, forming mature intestinal structures with functional cell types and digestive capabilities, as demonstrated in a mouse model.

These HIOs not only replicate the architecture of the human intestine but also respond to systemic signals from the host, indicating their potential for studying intestinal physiology and diseases, as well as for therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vivo model of human small intestine using pluripotent stem cells. Watson, CL., Mahe, MM., Múnera, J., et al.[2023]

Research has shifted focus from bone marrow-derived cells to cardiac atrial stem cells (CASCs) for heart regeneration, as CASCs show a much higher potential for differentiation into mature heart cells (98%).

Clinical trials have shown that while traditional methods using bone marrow cells only provide minor improvements in heart function, CASCs significantly enhance both regional and global left ventricular ejection fraction, indicating a more effective approach to cardiac repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From Bone Marrow to Cardiac Atrial Appendage Stem Cells for Cardiac Repair: A Review. Hendrikx, M., Fanton, Y., Willems, L., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12512236/

Advances in Nutritional and Therapeutic Strategies for Type 2 ... This narrative review aims to examine the nutritional consequences of type 2 intestinal failure (T2IF), assess current nutritional therapies ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2950456225000156

A comparison of chyme reinfusion therapy methods Recently, innovative technology has demonstrated enhanced intestinal absorption and decreased intestinal losses, associated with improved nutritional and ...

3. theinsides.co theinsides.co/blog/what-is-chyme-reinfusion

What is Chyme Reinfusion? Chyme Reinfusion enables patients to reestablish oral feeding and wean off the Parenteral Nutrition (PN) in as little as 3 days (1), resulting in significant ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06751628/prospective-study-of-the-methods-and-outcomes-of-chyme-reinstillation-after-small-bowel-surgery

Prospective Study of the Methods and Outcomes ... Such solutions could mitigate intestinal failure, reduce PN reliance, prevent dehydration and kidney failure, shorten hospital stays, and ...

5. nice.org.uk nice.org.uk/guidance/mib286/resources/the-insides-system-for-managing-intestinal-failure-pdf-2285965878170821

The Insides System for managing intestinal failure It is used for managing acute severe intestinal failure (type 2) after bowel surgery. • The innovative aspects are that it is a chyme reinfusion ...

6. theinsides.co theinsides.co/clinical-publication/chyme-reinfusion-for-small-bowel-double-enterostomies-and-enteroatmospheric-fistulas-in-adult-patients-a-systematic-review

Chyme Reinfusion for Small Bowel Double Enterostomies ... This review aimed to critically assess the literature regarding chyme reinfusion (CR) to define its current status and future directions.

7. clinicalnutritionespen.com clinicalnutritionespen.com/article/S2405-4577(23)02026-0/fulltext

Chyme reinfusion with the insides system®: Case series ... The INSIDES System is a safe, efficient tool for management of IF type2 for carefully chosen patients with a need of training period for a least one week.

8. intestinalfailurejournal.org intestinalfailurejournal.org/article/S2950-4562(25)00015-6/pdf

A comparison of chyme reinfusion therapy methods Patients with high output enterostomies are at risk of intestinal failure (IF) from short bowel syndrome (SBS) when a significant portion of the ...