MFGM-EnhaNceD RUTF for Children With SAM
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,600
- 试验地点
- 10
- 主要终点
- Malawi Developmental Assessment Tool global z-score
研究概览
简要总结
The goal of this clinical trial is to test the use of milk fat globule membrane (MFGM) in ready-to-use therapeutic food (RUTF) in children with severe acute malnutrition in Sierra Leone. The main questions it aims to answer are:
- Will the inclusion of MFGM in RUTF for 6-59-month-old Sierra Leonean children with severe acute malnutrition improve their neurodevelopment?
- Will the inclusion of MFGM in RUTF for 6-59-month-old Sierra Leonean children with severe acute malnutrition reduce its worst consequences: death, hospitalization, and remaining severely malnourished despite treatment?
Researchers will compare the MFGM-containing RUTF to standard RUTF, which contains skim milk powder.
Participants will:
- undergo measurement of length, weight, mid-upper arm circumference, and nutritional edema assessment every two weeks during severe malnutrition treatment
- be treated with either MFGM-RUTF or standard RUTF at a dose of 2 sachets per day for up to 12 weeks
- undergo neurodevelopmental testing using the Malawi Developmental Assessment Tool at the end of SAM treatment and 6 months later
- a subset of participants will undergo blood spot collection and stool sample collection
详细描述
Globally, approximately 15 million children are suffering from severe acute malnutrition (SAM) at any one time, a number that has not declined in recent decades despite significant technological advancements in agriculture and food science. SAM is a condition of total-body depletion of the nutrients required for health and development; without treatment, 50% of affected children will die. Whereas historically children with SAM were admitted to and treated within hospitals, the advent of ready-to-use therapeutic food (RUTF) and community-based management of acute malnutrition revolutionized SAM care by allowing it to occur safely and successfully by the child's caregiver in their own home.
RUTF was designed to provide the nutrients required for physical recovery in a safe, palatable format. It is equal parts peanut paste, sugar, vegetable oil, and skim milk powder, with added micronutrients and emulsifier. At inception, attention was not specifically paid to how RUTF's composition might impact neurodevelopmental recovery in children with SAM. Research over the past decade has revealed that even following successful treatment with RUTF, children diagnosed with SAM still score 1-3 standard deviations below age-based expectations on neurodevelopmental tests. This suggests that the nutrient profile of standard RUTF is not sufficient to recover the developmental damage incurred by SAM.
Recently, progress has been made toward improving the developmental trajectory of children with SAM by altering RUTF. A randomized, blinded trial in Malawi including 2,500 children with SAM showed that improving the polyunsaturated fatty acid (PUFA) profile of RUTF by reducing linoleic acid and adding docosahexaenoic acid (DHA) yields superior neurodevelopment 6 months after treatment, by 0.19 standard deviations on a standardized, culturally adapted neurodevelopmental test. This demonstrates that neurodevelopmental recovery in SAM is sensitive to the lipid profile of RUTF. Despite the benefits of improved PUFA RUTF, however, children with SAM remained 1 standard deviation below expectations in neurodevelopment.
The milk fat globule membrane (MFGM) in mammalian milk contains a host of nutrients and bioactive compounds supportive of physical health and brain development. Bovine MFGM added to infant formula has been tested in several clinical trials and has demonstrated a reduction in infectious episodes, such as diarrhea and ear infections, as well as improvement in cognitive development, compared with infant formula not containing MFGM. In these trials and others, MFGM has been shown to be safe and well-tolerated. Currently, RUTF contains skim milk powder as its high-quality protein source, and peanut and vegetable oils as the primary sources of fat. These vegetable fat sources are deficient in the lipids provided by MFGM: sphingolipids, cholesterol, and other phospholipids such as phosphatidylcholine and phosphatidylethanolamine, all of which play roles in brain development. It is possible that the lipids contained in MFGM may further support neurodevelopmental recovery in SAM children.
By acting as a natural emulsifier, MFGM also offers a food formulation advantage that is relevant to children with SAM. Animal model studies have demonstrated that emulsifiers can compromise the gut barrier. Children with SAM have damaged small intestinal barrier function, which can lead to translocation of gut bacteria and resulting systemic infection. As RUTF will compose nearly 100% of a child's intake for the duration of treatment - up to 3 months - it is possible that inclusion of emulsifier may impede gut healing and recovery. Considering this concern, the Manary lab ran a clinical trial in 2018-2019 testing a novel formulation of RUTF designed with oat in place of some skim milk powder and peanut, and without hydrogenated vegetable oil (standard emulsifier), because oat acts as a natural emulsifier. In this trial, children with SAM receiving the oat-RUTF had 10% absolute higher recovery and a 33% relative reduction in the worst SAM outcomes (death, hospitalization, or remaining severely malnourished). Like oat, MFGM in RUTF allows for omission of emulsifier and may yield similar benefits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Months 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •6-59 months of age
- •Reside within the catchment area of a participating clinic
- •mid-upper arm circumference < 11.5 cm and/or weight-for-length z-score < -3 and/or presence of bilateral pedal pitting edema
- •willingness to comply with all study procedures and availability for the duration of the study, including no plan to move from the catchment area of a participating clinic
排除标准
- •Features of complicated SAM: inability to tolerate a 30 g test dose of RUTF, breathing difficulties, mental status changes, sepsis, diarrhea with severe dehydration, and/or physician/nursing clinical assessment that the child needs immediate hospitalization
- •Participation in a separate therapeutic feeding program within the past month
- •Known allergy to study food ingredient (peanut, milk, fish)
- •Clinically evident developmental delay (most often determined based on research nursing assessment of physical appearance, movement, and informal discussion with caregiver)
- •Presence of a chronic severe medical condition (other than tuberculosis and HIV), such as congenital heart disease
研究组 & 干预措施
MFGM-RUTF (Milk fat globule membrane ready-to-use therapeutic food)
One sachet contains 92g of MFGM-RUTF. During SAM treatment, each participant will be given sufficient MFGM-RUTF to consume 2 sachets per day, which will provide approximately 1000 calories, 27g of protein, 63g of fat, and over 1 RDA of micronutrients.
干预措施: MFGM-RUTF (milk fat globule membrane ready-to-use therapeutic food) (Dietary Supplement)
MFGM-RUTF (Milk fat globule membrane ready-to-use therapeutic food)
One sachet contains 92g of MFGM-RUTF. During SAM treatment, each participant will be given sufficient MFGM-RUTF to consume 2 sachets per day, which will provide approximately 1000 calories, 27g of protein, 63g of fat, and over 1 RDA of micronutrients.
干预措施: Amoxicillin (Drug)
MFGM-RUTF (Milk fat globule membrane ready-to-use therapeutic food)
One sachet contains 92g of MFGM-RUTF. During SAM treatment, each participant will be given sufficient MFGM-RUTF to consume 2 sachets per day, which will provide approximately 1000 calories, 27g of protein, 63g of fat, and over 1 RDA of micronutrients.
干预措施: Sulfadoxine (12.5 mg)/Pyrimethamine (250 mg) (Drug)
S-RUTF (standard ready-to-use therapeutic food)
One sachet contains 92g of S-RUTF. During SAM treatment, each participant will be given sufficient S-RUTF to consume 2 sachets per day, which will provide approximately 1000 calories, 27g of protein, 60g of fat, and over 1 RDA of micronutrients.
干预措施: S-RUTF (standard ready-to-use therapeutic food) (Dietary Supplement)
S-RUTF (standard ready-to-use therapeutic food)
One sachet contains 92g of S-RUTF. During SAM treatment, each participant will be given sufficient S-RUTF to consume 2 sachets per day, which will provide approximately 1000 calories, 27g of protein, 60g of fat, and over 1 RDA of micronutrients.
干预措施: Amoxicillin (Drug)
S-RUTF (standard ready-to-use therapeutic food)
One sachet contains 92g of S-RUTF. During SAM treatment, each participant will be given sufficient S-RUTF to consume 2 sachets per day, which will provide approximately 1000 calories, 27g of protein, 60g of fat, and over 1 RDA of micronutrients.
干预措施: Sulfadoxine (12.5 mg)/Pyrimethamine (250 mg) (Drug)
结局指标
主要结局
Malawi Developmental Assessment Tool global z-score
时间窗: 6 (5-7) months after SAM treatment completion
Age-standardized score, -6 to +6, higher scores are better
Composite of poor severe acute malnutrition treatment outcomes
时间窗: 2-12 weeks of therapeutic feeding
This composite outcome will include death, hospitalization, and remaining severely malnourished despite 12 weeks of treatment
次要结局
- Malawi Developmental Assessment Tool gross motor domain z-score(Within 1 month of SAM treatment completion)
- Malawi Developmental Assessment Tool fine motor domain z-score(Within 1 month of SAM treatment completion)
- Malawi Developmental Assessment Tool global z-score(Within 1 month of SAM treatment completion)
- Malawi Developmental Assessment Tool language domain z-score(Within 1 month of SAM treatment completion)
- Malawi Developmental Assessment Tool social-emotional domain z-score(Within 1 month of SAM treatment completion)
- Remaining severely malnourished at end of SAM treatment(12 weeks of therapeutic feeding)
- Death during SAM treatment(2-12 weeks of therapeutic feeding)
- Hospitalization during SAM treatment(2-12 weeks of therapeutic feeding)
- Graduation from SAM treatment(2-12 weeks of therapeutic feeding)
- Rate of weight change(Across initial 4 weeks of therapeutic feeding, or 2 weeks if graduate after 2 weeks)
- Rate of length change(Across 2-12 weeks of therapeutic feeding)
- Rate of mid-upper arm circumference change(Across 2-12 weeks of therapeutic feeding)
- Rate of change in length-for-age z-score across entire follow-up(7-10 months (2-12 weeks of therapeutic feeding, 5-7 months of follow-up thereafter))
- Diarrhea incidence during SAM treatment(2-12 weeks of therapeutic feeding)
- Fever incidence during SAM treatment(2-12 weeks of therapeutic feeding)
- Plasma DHA status at end of SAM treatment(Collected after 2-12 weeks of therapeutic feeding)
- Fecal host mRNA transcripts as markers of environmental enteric dysfunction at end of SAM treatment(Collected after 2-12 weeks of therapeutic feeding)
- Malawi Developmental Assessment Tool global z-score trajectory(6 (5-7) months after SAM treatment completion)