Necrotizing EnterocolitisPhase 2NCT02796703
Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis
A Phase 2 study testing Heat Inactivated probiotics in people with Necrotizing Enterocolitis and Enterocolitis, Necrotizing, run by Shaare Zedek Medical Center at 1 site in Israel.
Trial summary
Prophylactic probiotics have been shown to decrease the incidence of Necrotizing Enterocolitis (NEC) in premature neonates. However, there is some resistance to giving live bacteria to small babies. Based on animal data, the investigators hypothesized that heat inactivated probiotics would also reduce NEC. Read more about this study
- Who is it for?
- Ages 6 hours to 7 days
- Conditions the study is for
- Necrotizing Enterocolitis, Enterocolitis, Necrotizing
- What is being tested?
- Heat Inactivated probiotics
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 450 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2016to Sep 2020
- Phase
- Phase 2
- 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 6 hours to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Preterm neonates
- ≤1500 gm birth weight
Who cannot join
- Infants who are not deemed likely to survive more than one week;
- Infants who are not started on enteral feeds by one week of age;
- Infants who have significant congenital malformations or other gastrointestinal problem
Trial locations and contacts
1 site in 1 country.
Israel1 site
Neonatal Intensive Care Unit - Shaare Zedek Medical Center
Jerusalem, 91031
About this study
Official title: Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis (NEC) in Premature Neonates
Prophylactic probiotics have been shown to decrease the incidence of Necrotizing Enterocolitis (NEC) in premature neonates. However, there is some resistance to giving live bacteria to small babies. Based on animal data, the investigators hypothesized that heat inactivated probiotics would also reduce NEC.
Read the detailed description
Preterm neonates, <1500 gm birth weight will potentially be candidates for study and will be recruited when they begin enteral feeding. The infants will be prospectively and randomly assigned to one of two groups:
- Treatment group - to receive daily inactivated probiotic prophylaxis starting with the initiation of feeds. 1 tsp powder will be diluted in 2 cc of mother's milk when possible or in Similac Special Care formula 24 cal when mother's milk is not available; and
- Control group - to receive 2 cc/day of placebo similarly diluted. Supplements will be continued until the infant tolerates enteral feeds of 100 cc/kg/day or reaches 35 weeks post conceptual age (whichever comes LAST). Biotikid, a probiotic mixture, will be heated to 100 degrees C for 10 minutes. Babies will be followed clinically for signs of NEC, and with urine intestinal fatty acid binding protein (IFABP) and fecal calprotectin levels.
The investigators primary aim is to demonstrate that premature neonates who are treated prophylactically with heat inactivated probiotics will have less necrotizing enterocolitis when compared to age matched infants given placebo.
The investigators secondary objectives are to demonstrate the following:
- That the decrease in NEC will coincide with improved intestinal barrier integrity, as reflected by levels of:
- I-FABP in urine
- Fecal Calprotectin
- Being tested
- Heat Inactivated probiotics, Placebo
- Medical subject headings
- Enterocolitis, Necrotizing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Heat Inactivated probioticsDietary supplement
Biotikid, a probiotic mixture, will be heated to 100 degrees Centigrade for 10 minutes to inactivate and then 1 tsp will be diluted in milk and give with feeds to treatment group
PlaceboDietary supplement
2 cc of milk will be given to control group
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Placebo comparator | Dietary Supplement: Placebo 2 cc/day of placebo diluted in mother's milk (when available) or premature formula. Receives: Dietary Supplement: Placebo |
| Treatment Group | Active comparator | Dietary Supplement: Heat Inactivated Probiotics
1 tsp heat inactivated Biotikid powder will be diluted in 2 cc of mother's milk (when available) or premature formula. Receives: Dietary Supplement: Heat Inactivated probiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Necrotizing Enterocolitis, Bell Stage 2 or above, or Death
Necrotizing Enterocolitis diagnosis will be based on clinical and radiographic criteria
Measured: Birth until 40 weeks post-conceptional age
Secondary outcomes (2)
Increased Urine IFABP Levels
Measured: Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age
Increased Fecal Calprotectin Levels
Measured: Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionJul 2020 (estimated)
- Study completionSep 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Necrotizing EnterocolitisStudies of the same condition, open and under way.
- 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shaare Zedek Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cathy Hammerman, Shaare Zedek Medical Center
- Investigators
- Cathy Hammerman, MD, Principal investigator, Shaare Zedek Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02796703
- Sponsor's protocol ID
- SZMC 0297-15
- Status last verified
- Jun 2016
- First submitted
- 22 May 2016
- Last updated
- 16 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Awad H, Mokhtar H, Imam SS, Gad GI, Hafez H, Aboushady N. Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. Pak J Biol Sci. 2010 Mar 15;13(6):253-62. doi: 10.3923/pjbs.2010.253.262.
PubMed 20506712
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis (NEC) in Premature Neonates
- ClinicalTrials.gov ID
- NCT02796703
- Acronym / sponsor ID
- SZMC 0297-15
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Shaare Zedek Medical CenterUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Sep 2020 (estimated)
- First posted
- 13 Jun 2016 (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.
Prophylactic probiotics have been shown to decrease the incidence of Necrotizing Enterocolitis (NEC) in premature neonates. However, there is some resistance to giving live bacteria to small babies. Based on animal data, the investigators hypothesized that heat inactivated probiotics would also reduce NEC.
Detailed description
Preterm neonates, <1500 gm birth weight will potentially be candidates for study and will be recruited when they begin enteral feeding. The infants will be prospectively and randomly assigned to one of two groups:
- Treatment group - to receive daily inactivated probiotic prophylaxis starting with the initiation of feeds. 1 tsp powder will be diluted in 2 cc of mother's milk when possible or in Similac Special Care formula 24 cal when mother's milk is not available; and
- Control group - to receive 2 cc/day of placebo similarly diluted. Supplements will be continued until the infant tolerates enteral feeds of 100 cc/kg/day or reaches 35 weeks post conceptual age (whichever comes LAST). Biotikid, a probiotic mixture, will be heated to 100 degrees C for 10 minutes. Babies will be followed clinically for signs of NEC, and with urine intestinal fatty acid binding protein (IFABP) and fecal calprotectin levels.
The investigators primary aim is to demonstrate that premature neonates who are treated prophylactically with heat inactivated probiotics will have less necrotizing enterocolitis when compared to age matched infants given placebo.
The investigators secondary objectives are to demonstrate the following:
- That the decrease in NEC will coincide with improved intestinal barrier integrity, as reflected by levels of:
- I-FABP in urine
- Fecal Calprotectin
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Placebo comparator | Dietary Supplement: PlaceboDietary Supplement: Placebo 2 cc/day of placebo diluted in mother's milk (when available) or premature formula. |
| Treatment Group | Active comparator | Dietary Supplement: Heat Inactivated probioticsDietary Supplement: Heat Inactivated Probiotics 1 tsp heat inactivated Biotikid powder will be diluted in 2 cc of mother's milk (when available) or premature formula. |
Who may qualify
- Ages
- 6 hours to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Preterm neonates
- ≤1500 gm birth weight
Key exclusion criteria (3 listed)
- Infants who are not deemed likely to survive more than one week;
- Infants who are not started on enteral feeds by one week of age;
- Infants who have significant congenital malformations or other gastrointestinal problem
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 |
|---|---|---|
| Heat Inactivated probioticsBiotikid, a probiotic mixture, will be heated to 100 degrees Centigrade for 10 minutes to inactivate and then 1 tsp will be diluted in milk and give with feeds to treatment group | Dietary supplement | Treatment Group |
| Placebo2 cc of milk will be given to control group | Dietary supplement | Control Group |
Primary outcome
Necrotizing Enterocolitis, Bell Stage 2 or above, or Death
Time frame: Birth until 40 weeks post-conceptional age
Necrotizing Enterocolitis diagnosis will be based on clinical and radiographic criteria
2 secondary outcomes
Increased Urine IFABP Levels
Time frame: Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age
Increased Fecal Calprotectin Levels
Time frame: Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2016.
- Background: PubMed 20506712Awad H, Mokhtar H, Imam SS, Gad GI, Hafez H, Aboushady N. Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. Pak J Biol Sci. 2010 Mar 15;13(6):253-62. doi: 10.3923/pjbs.2010.253.262.
- Individual participant dataSharing planned: No
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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.
Cathy Hammerman, MD principal investigator
Shaare Zedek Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Heat Inactivated probiotics in people with Necrotizing Enterocolitis and Enterocolitis, Necrotizing, run by Shaare Zedek Medical Center at 1 site in Israel.
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 2 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 16 Jun 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 Israel. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cathy Hammerman, MD (0508685238, cathyh@ekmd.huji.ac.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Necrotizing Enterocolitis, Bell Stage 2 or above, or Death (time frame: Birth until 40 weeks post-conceptional age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02796703, which also lists 1 linked publication.
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 16 Jun 2016.