Hypoallergenic and Anti-inflammatory Feeds in Malawian Children With Severe Acute Malnutrition (SAM) (SAM)

• ClinicalTrials.gov Identifier: NCT02639416
• Recruitment Status: Completed
• First Posted: December 24, 2015
• Last Update Posted: February 25, 2021
• Sponsor: Liverpool School of Tropical Medicine
• Collaborators: University of Toronto; University of Malawi College of Medicine; Queen Elizabeth Central Hospital, Blantyre, Malawi
• Information provided by (Responsible Party): Liverpool School of Tropical Medicine

Tracking Information

• First Submitted Date: December 21, 2015
• First Posted Date: December 24, 2015
• Last Update Posted Date: February 25, 2021
• Actual Study Start Date: January 1, 2016
• Actual Primary Completion Date: January 11, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 23, 2015)

Change in faecal calprotectin [ Time Frame: 14 days ]

Validated marker of intestinal inflammation

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 23, 2015)

• Days with diarrhoea [ Time Frame: 1-14 days ]
  number of days with 3 or more loose/watery stools
• Weight gain [ Time Frame: 1-14 days ]
  change in weight in g/kg/day
• Episodes of sepsis [ Time Frame: 1-14 days ]
  Clinical diagnosis
• Death [ Time Frame: 1-14 days ]
  number of children who die

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Hypoallergenic and Anti-inflammatory Feeds in Malawian Children With Severe Acute Malnutrition (SAM)
• Official Title: Hypoallergenic and Anti-inflammatory Feeds to Treat Intestinal Inflammation in Malawian Children With Severe Acute Malnutrition: A Pilot Randomized Controlled Clinical Trial (SAM)

Brief Summary

Children with complicated severe acute malnutrition (SAM), such as inability to take adequate feeds, infection and diarrhoea, require in-patient management. Despite following a well-established World Health Organisation (WHO) protocol, outcomes are poor. Case fatality often exceeds 20%. Amongst survivors discharged home, many subsequently die, have long-term poor growth or recurrence of SAM.

It has long been recognized that children with SAM have intestinal inflammation and that this persists despite management according to WHO guidelines. The inflammation is thought to result from increased exposure to microbial pathogens in the gut in areas with poor sanitation. The damaged lining of the intestine impairs food digestion and absorption, likely allows gut bacteria to enter the blood stream to cause sepsis and also exposes the gut immune cells to microbial and food antigens causing the inflammation to persist. Failure to treat the intestinal inflammation is likely to contribute to the poor response to treatment and poor long-term outcomes in many children with SAM.

The intestinal inflammation seen in SAM is very similar to that which occurs in food intolerance (e.g. intolerance to cow's milk protein) and inflammatory bowel disease. In these conditions, the inflammation is treated very effectively with hypoallergenic ("elemental") and anti-inflammatory ("polymeric") formulas. These are nutritionally complete feeds that have a similar composition to the feeds used for nutritional rehabilitation in SAM.

We aim to undertake a pilot study to see if an elemental and/or polymeric formula are tolerated by children with SAM and help to reduce intestinal inflammation. We also aim to learn more about the intestinal inflammation in general that occurs in SAM by observing carefully the effect of these specific formulae and to do in-depth metabolic analyses.

• Detailed Description: We will study children admitted to the Moyo ward at the Queen Elizabeth Central Hospital, Blantyre, Malawi with complicated SAM. Following informed consent, children will be recruited once they have completed the initial stabilisation phase of management and enter the transition phase to nutritional rehabilitation. They will be randomly allocated to one of 3 arms, either 1) standard feeds (F-100 and/or ready-to-use therapeutic feeds), 2) a polymeric therapeutic formula or 3) an elemental therapeutic formula. The alternative feeds will be supplemented with micronutrients to be equivalent in composition to F-100. All children will remain admitted to the ward for 2 weeks and receive exclusively the allocated formula. All other aspects of the management of SAM will follow current practice based on WHO guidelines.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Severe Malnutrition
• Enteritis

Intervention

• Dietary Supplement: Polymeric formula
  Polymeric formulae are recommended in the management of inflammatory bowel disease in children
• Dietary Supplement: Elemental formula
  Elemental formulae are recommended in cow's milk and other food intolerances in children.
• Other: Standard management
  Standard management with F-100 and/or RUTF

Study Arms

• Active Comparator: Standard management
  Standard management consists of F-100 and/or ready-to-use therapeutic food (RUTF) according to usual practice for 14 days
  Intervention: Other: Standard management
• Experimental: Polymeric formula
  Exclusive polymeric formula supplemented with micronutrients in equivalent volume to F-100 for 14 days
  Intervention: Dietary Supplement: Polymeric formula
• Experimental: Elemental formula
  Exclusive elemental formula supplemented with micronutrients in equivalent volume to F-100 for 14 days
  Intervention: Dietary Supplement: Elemental formula

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 23, 2021): 95
• Original Estimated Enrollment (submitted: December 23, 2015): 120
• Actual Study Completion Date: January 11, 2017
• Actual Primary Completion Date: January 11, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 6-23 months
• SAM diagnosed according to WHO criteria: (Weight-for-height z score <-3 and/or mid-upper arm circumference <11.5 cms and/or nutritional oedema)
• Admitted to hospital because of SAM with medical complications or fails an appetite test
• Completed stabilization phase and entering the second phase in refeeding; the transition Phase
• Willing to stay on the ward for 2 weeks after the stabilization phase (travel expenses will be provided)

Exclusion Criteria:

• Specific cause of malnutrition (e.g. cerebral palsy, other organ disease)
• Sibling admitted with SAM at the same time
• Unwilling to stay on ward for at least 2 weeks
• Declined to give consent
• Participating in another study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 23 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Malawi

Administrative Information

• NCT Number: NCT02639416
• Other Study ID Numbers: 15.048
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Liverpool School of Tropical Medicine
• Study Sponsor: Liverpool School of Tropical Medicine

Collaborators

• University of Toronto
• University of Malawi College of Medicine
• Queen Elizabeth Central Hospital, Blantyre, Malawi

Investigators

• Principal Investigator: Stephen J Allen, MD; Liverpool School of Tropical Medicine

• PRS Account: Liverpool School of Tropical Medicine
• Verification Date: February 2021