Very Low Birth Weight PretermsPhase 2/3NEOTRANSNCT01536483
Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1250 Grams
A Phase 2/3 study testing Butyrate enemas in people with Very Low Birth Weight Preterms, run by Nantes University Hospital at 1 site in France.
Trial summary
Clinical management of very low birth weight newborns (VLBW <1250g) consists in several challenges to adapt immature physiological systems to extrauterine life. Advances in neonatal medicine for pulmonary and/or neurological and/or cardiovascular diseases have significantly improved outcomes of these children. Read more about this study
- Who is it for?
- Ages 5 to 5 days
- Conditions the study is for
- Very Low Birth Weight Preterms
- What is being tested?
- Butyrate enemas
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2012to Mar 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 5 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Any preterm infant with a birth weight less than or equal to 1250 grams admitted in the neonatal intensive care unit of Nantes Hospital
- Inborn or outborn
- No signs of gastrointestinal perforation or ECUN
- Absence of severe congenital disease
- Written informed consent of parental authority.
Who cannot join
- Newborn with birth weight greater than 1250 grams,
- Gestational age > 30 AG
- Digestive pathology diagnosed prior PND5: perforation, necrotizing enterocolitis, malformations
- Severe congenital pathology inconsistent with clinical assessment.
- Parental Refusal
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1250 Grams. Clinical Trial Prospective, Monocentric, Randomized in Double-blinded.
Clinical management of very low birth weight newborns (VLBW <1250g) consists in several challenges to adapt immature physiological systems to extrauterine life. Advances in neonatal medicine for pulmonary and/or neurological and/or cardiovascular diseases have significantly improved outcomes of these children. However, the gastro-intestinal (GI) tract remains a major cause of morbidity due to
- the immaturity of GI functions (prolonged ileus, bacterial overgrowth and translocation),
- the complication of GI tract immaturity: intestinal perforation and enterocolitis necrotizing)
- the need of a prolonged parenteral nutrition and its complications (central venous catheter infections, sepsis, electrolyte disturbances) but without generate a high proof level on this targeted population (<1250g).
Read more
The GI functions are progressively acquired during development and are largely sensitive to the environment, especially the intestinal luminal content. Indeed, probiotics and prebiotics have shown beneficial effects upon GI functions of newborns. One of the metabolite of the gut flora potentially involved is the butyrate. Butyrate is a short chain fatty acid produced in the colon by the microbiota (carbo-hydrates degradation). The colonic amount of butyrate increases gradually after birth. The beneficial effects of butyrate are related to its properties upon the epithelial barrier (anti-inflammatory, antioxidant, barrier repair) and upon the enteric nervous system (network of neurons and glial cells) that regulate GI functions and in particular colonic motility.
To date, there is no clinical consensus to manage digestive disorders of VLBW. Several clinical studies have assessed the effects of prokinetic drugs, dietary supplements (probiotics, prebiotics) but without generate a high proof level on this targeted population. In this context, a recent study of our Research Unit (INSERM-CIC Mère-Enfant 004) has shown benefit effects of oral probiotics supplementation in children with birth weight greater than 1000g but not in extreme preterms with birth weight less than 1000g.
The main hypothesis to explain theses results lies in the intensive use of antibiotic and feeding interruption frequency in this targeted population which induce disturbances in the composition of the gut lumen (in particular the flora).
Colonic enemas assessed in various observational studies concerning VLBW seem to demonstrate a clinical efficiency upon the colonic transit, underlying by mechanical and osmotic mechanisms.
Here, the investigators propose to evaluate the clinical efficiency of butyrate enemas by a prospective randomized clinical trial blinded design.
The purpose of NEOTRANS study is to demonstrate that butyrate enemas may improve the nutritional management of extreme preterm less than 1250 grams, by facilitating the development of colic motility and clinical nutrition tolerance.
- Conditions
- Very Low Birth Weight Preterms
- Being tested
- Butyrate enemas
- Keywords
- Butyrate, Preterms, Very Low Birth Weight (<1250g), Rectocolonic enemas, Digestive maturation, Parenteral nutrition weaning, ECUN, Whole gut transit time
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Butyrate enemasDrug
Seven enemas
- Possibility to delay from 24 to 48 hours the procedure in case of clinical poor tolerance(maximum two enemas postponed and delayed at PND12 and PND13)
- The study remains blinded for the investigation team through the intervention of a clinical research nurse
- According to the procedure previously described by Nakaoka et al. (2009), a lubricated Foley catheter Ch 6 will be introduced into the rectum, the balloon will be inflated with 1 ml water for injections. Butyrate solution will be placed in a bag placed 50 cm above the child. Therefore, treatment administration will be performed at a controlled pressure of 50 cm H2O without any manual intervention
- Installation time and retention is setted at 15 minutes
- Treatment units will be directly placed in the incubator 30 min before the procedure to warm the enema to +36°C
- Per-treatment clinical monitoring of the tolerance will be performed by a neonatologist
| Study group | Role | What they receive |
|---|---|---|
| Butyrate | Experimental | New born with a birth weight <1000g: Seven enemas of butyrate will be performed every 2 days from PND5
New born with a birth weight >1000g: Seven enemas of butyrate will be performed every day from PND5 Receives: Drug: Butyrate enemas |
| Therapeutic Abstention | No intervention | The protocol will pretend enema: instillation in the diaper the product under consideration, to make the two indistinguishable processes (time, odor, wicking diaper ...) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of colonic butyrate enemas in digestive maturation of preterms
The primary outcome of NEOTRANS study consists in the evaluation of the effects of colonic butyrate enemas upon the digestive maturation of preterms.
This endpoint is based on a clinical criteria that is the delay of weaning of the parenteral nutrition support. An increase of 25% (50 vs 75%) will be considered clinically significant.
Parenteral nutrition weaning is defined as the day where enteral caloric intake reach 80% of total calories.
Measured: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Secondary outcomes (9)
Gastrointestinal complications frequency
Measured: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Nosocomial infections frequency
Measured: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Iatrogenic effect
Measured: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
whole gut transit time (red carmine test)
Measured: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Growth
Comparaison between 2 arms of height, weight and head circumference
Measured: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Invasive ventilation support
Measured: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Bronchopulmonary dysplasia incidence
Measured: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Hospitalization duration
Measured: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Neuromotor development
ASQ questionnaire
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2012 (estimated)
- Study startFeb 2012
- Primary completionMar 2016
- Study completionMar 2016
Why it stopped: The second intermediary analysis showed no significant difference between both arms
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Very Low Birth Weight PretermsStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01536483
- Sponsor's protocol ID
- BRD/10/04-H
- Acronym
- NEOTRANS
- Status last verified
- May 2016
- First submitted
- 16 Feb 2012
- Last updated
- 11 May 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1250 Grams. Clinical Trial Prospective, Monocentric, Randomized in Double-blinded.
- ClinicalTrials.gov ID
- NCT01536483
- Acronym / sponsor ID
- NEOTRANS / BRD/10/04-H
- Conditions
- Very Low Birth Weight Preterms
- Keywords
- Butyrate, Preterms, Very Low Birth Weight (<1250g), Rectocolonic enemas, Digestive maturation, Parenteral nutrition weaning, ECUN, Whole gut transit time
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The second intermediary analysis showed no significant difference between both arms
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 22 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clinical management of very low birth weight newborns (VLBW <1250g) consists in several challenges to adapt immature physiological systems to extrauterine life. Advances in neonatal medicine for pulmonary and/or neurological and/or cardiovascular diseases have significantly improved outcomes of these children. However, the gastro-intestinal (GI) tract remains a major cause of morbidity due to
- the immaturity of GI functions (prolonged ileus, bacterial overgrowth and translocation),
- the complication of GI tract immaturity: intestinal perforation and enterocolitis necrotizing)
- the need of a prolonged parenteral nutrition and its complications (central venous catheter infections, sepsis, electrolyte disturbances) but without generate a high proof level on this targeted population (<1250g).
The GI functions are progressively acquired during development and are largely sensitive to the environment, especially the intestinal luminal content. Indeed, probiotics and prebiotics have shown beneficial effects upon GI functions of newborns. One of the metabolite of the gut flora potentially involved is the butyrate. Butyrate is a short chain fatty acid produced in the colon by the microbiota (carbo-hydrates degradation). The colonic amount of butyrate increases gradually after birth. The beneficial effects of butyrate are related to its properties upon the epithelial barrier (anti-inflammatory, antioxidant, barrier repair) and upon the enteric nervous system (network of neurons and glial cells) that regulate GI functions and in particular colonic motility.
To date, there is no clinical consensus to manage digestive disorders of VLBW. Several clinical studies have assessed the effects of prokinetic drugs, dietary supplements (probiotics, prebiotics) but without generate a high proof level on this targeted population. In this context, a recent study of our Research Unit (INSERM-CIC Mère-Enfant 004) has shown benefit effects of oral probiotics supplementation in children with birth weight greater than 1000g but not in extreme preterms with birth weight less than 1000g.
The main hypothesis to explain theses results lies in the intensive use of antibiotic and feeding interruption frequency in this targeted population which induce disturbances in the composition of the gut lumen (in particular the flora).
Colonic enemas assessed in various observational studies concerning VLBW seem to demonstrate a clinical efficiency upon the colonic transit, underlying by mechanical and osmotic mechanisms.
Here, the investigators propose to evaluate the clinical efficiency of butyrate enemas by a prospective randomized clinical trial blinded design.
The purpose of NEOTRANS study is to demonstrate that butyrate enemas may improve the nutritional management of extreme preterm less than 1250 grams, by facilitating the development of colic motility and clinical nutrition tolerance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Butyrate | Experimental | Drug: Butyrate enemasNew born with a birth weight <1000g: Seven enemas of butyrate will be performed every 2 days from PND5 New born with a birth weight >1000g: Seven enemas of butyrate will be performed every day from PND5 |
| Therapeutic Abstention | No intervention | –The protocol will pretend enema: instillation in the diaper the product under consideration, to make the two indistinguishable processes (time, odor, wicking diaper ...) |
Who may qualify
- Ages
- 5 to 5 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Any preterm infant with a birth weight less than or equal to 1250 grams admitted in the neonatal intensive care unit of Nantes Hospital
- Inborn or outborn
- No signs of gastrointestinal perforation or ECUN
- Absence of severe congenital disease
- Written informed consent of parental authority.
Key exclusion criteria (5 listed)
- Newborn with birth weight greater than 1250 grams,
- Gestational age > 30 AG
- Digestive pathology diagnosed prior PND5: perforation, necrotizing enterocolitis, malformations
- Severe congenital pathology inconsistent with clinical assessment.
- Parental Refusal
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Butyrate enemasSeven enemas * Possibility to delay from 24 to 48 hours the procedure in case of clinical poor tolerance(maximum two enemas postponed and delayed at PND12 and PND13) * The study remains blinded for the investigation team through the intervention of a clinical research nurse * According to the procedure previously described by Nakaoka et al. (2009), a lubricated Foley catheter Ch 6 will be introduced into the rectum, the balloon will be inflated with 1 ml water for injections. Butyrate solution will be placed in a bag placed 50 cm above the child. Therefore, treatment administration will be performed at a controlled pressure of 50 cm H2O without any manual intervention * Installation time and retention is setted at 15 minutes * Treatment units will be directly placed in the incubator 30 min before the procedure to warm the enema to +36°C * Per-treatment clinical monitoring of the tolerance will be performed by a neonatologist | Drug | Butyrate |
Primary outcome
Efficacy of colonic butyrate enemas in digestive maturation of preterms
Time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
The primary outcome of NEOTRANS study consists in the evaluation of the effects of colonic butyrate enemas upon the digestive maturation of preterms. This endpoint is based on a clinical criteria that is the delay of weaning of the parenteral nutrition support. An increase of 25% (50 vs 75%) will be considered clinically significant. Parenteral nutrition weaning is defined as the day where enteral caloric intake reach 80% of total calories.
9 secondary outcomes
Gastrointestinal complications frequency
Time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Nosocomial infections frequency
Time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Iatrogenic effect
Time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
whole gut transit time (red carmine test)
Time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Growth
Time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Invasive ventilation support
Time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Bronchopulmonary dysplasia incidence
Time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Hospitalization duration
Time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Neuromotor development
Time frame: 2 years
Results and safety
The study was stopped early (reason given: The second intermediary analysis showed no significant difference between both arms). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Butyrate enemas in people with Very Low Birth Weight Preterms, run by Nantes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The second intermediary analysis showed no significant difference between both arms). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of colonic butyrate enemas in digestive maturation of preterms (time frame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2016.