Prevention of Linear Growth Failure in Infants and Young Children With Lipid-based Nutrient Supplements (iLiNS-DOSE)

Sponsor

Tampere University (Other)

Overall Status

Completed

CT.gov ID

NCT00945698

Collaborator

University of Malawi College of Medicine (Other), University of California, Davis (Other), Bill and Melinda Gates Foundation (Other)

1,920

Enrollment

Location

Arms

Duration (Months)

33.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The use of lipid-based nutrients (LNS), such as Nutributter or fortified spread (FS), have been associated with improved growth and development outcomes among infants in Ghana and Malawi. Modified versions of such supplements have been developed to improve their nutrient density and quality and to lower their costs. Such modified products have proven acceptable to infants and their guardians in Malawi and Ghana. In the present trial, the investigator aim to identify the lowest growth-promoting daily dose of modified LNS. Additionally, the investigators will test a hypothesis that LNS that does not contain milk promotes growth as well as milk-containing LNS when given for 12 months at a 10-40 g daily dose to 6-18 month old infants in rural Malawi.

Condition or Disease	Intervention/Treatment	Phase
Malnutrition	Dietary Supplement: Lipid-based nutrient supplement, 10gM Dietary Supplement: Lipid-based nutrient supplement, 20gM Dietary Supplement: Lipid-based Nutrient Supplement, 20gNoM Dietary Supplement: Lipid-based nutrient supplement, 40gM Dietary Supplement: Lipid-based Nutrient Supplement, 40gNoM Dietary Supplement: Maize-soy flour	Phase 3

Detailed Description

Six-month old healthy infants are identified through community surveys in the study area. 1920 infants meeting set criteria are randomised into receiving the following intervention between 6 and 18 months of age: 1) standard treatment from 6-18 months (i.e.no supplements, with delayed intervention between 18-30 months of age (ST-DI), 2) 10 g / day milk-containing LNS (LNS-10gM), 3) 20 g / day milk-containing LNS (LNS-20gM), 4) 20 g / day milk-free LNS (LNS-20gNoM), 5) 40 g / day milk-containing LNS, (LNS-40gM) 6) 40 g / day milk-free LNS (LNS-40gNoM). The families receive the food supplements at 2-weekly intervals and the participants undergo a morbidity evaluation weekly, a limited development assessment at 4-weekly intervals and anthropometric evaluation at 26-week intervals and laboratory analyses at enrollment and at 18 months. Growth outcome analyses are done at 18 and at 42 months of age.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1920 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

A Two-centre, Randomised, Single-blind, Parallel Group Controlled Trial, Testing the Growth Promoting Effect of Long-term Complementary Feeding of Infants With Different Doses and Formulations of Lipid-based Nutrient Supplements (LNS)

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Aug 1, 2012

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: ST-DI (Delayed intervention) 1 kg fortified maize / soy flour (Likuni phala, LP) 2-weekly (71 g / day) between 18 and 30 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Maize-soy flour No food supplement during the primary trial period (6 to 18 months of age) 1 kg fortified maize / soy flour (Likuni phala, LP) 2-weekly (71 g / day) between 18 and 30 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-10gM 140 g of milk-containing LNS (LNS-10gM) 2-weekly (10 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based nutrient supplement, 10gM 140 g of milk-containing LNS (LNS-10gM) 2-weekly (10 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-20gM 280 g of milk-containing LNS (LNS-20gM) 2-weekly (20 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based nutrient supplement, 20gM 280 g of milk-containing LNS (LNS-20gM) 2-weekly (20 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-20gNoM 280 g of milk-free LNS (LNS-20gNoM) 2-weekly (20 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based Nutrient Supplement, 20gNoM 280 g of milk-free LNS (LNS-20gNoM) 2-weekly (20 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-40gM 560 g of milk-containing LNS (LNS-40gM) 2-weekly (40 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based nutrient supplement, 40gM 560 g of milk-containing LNS (LNS-40gM) 2-weekly (40 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring
Experimental: LNS-40gNoM 560 g of milk-free LNS (LNS-40gNoM) 2-weekly (40 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring	Dietary Supplement: Lipid-based Nutrient Supplement, 40gNoM 560 g of milk-free LNS (LNS-40gNoM) 2-weekly (40 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

Outcome Measures

Primary Outcome Measures

Change in length-for-age Z-score (LAZ, based on WHO 2005 MGRS) between enrollment and 18 months of age [Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months)]
Incidence of serious adverse events during the study period [12 months after enrollment (age 18 months)]

Secondary Outcome Measures

Change in weight-for-age (WAZ) and weight-for-length (WLZ) Z-scores [Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months)]
Incidence of stunting, underweight, and wasting [Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months)]
Prevalence of reduced appetite [Daily assessment during 12 month supplementation]
Energy intake from complementary foods [3 and 9 months after enrollment (age 9 and 15 months)]
Incidence of laboratory-confirmed malaria infection [12 months after enrollment (age 18 months)]
Incidence of caregiver-reported morbidity [Daily assessment during 12 month supplementation]
Immune function (measured by humoral immunity towards measles vaccination) [12 months after enrollment (age 18 months)]
Change in hemoglobin and micronutrient status (iron status, measured by zinc protoporphyrin (ZPP); plasma zinc; plasma vitamin A; B-vitamins and related metabolites; urine iodine [12 months after enrollment (age 18 months)]
Proportion with anaemia at 18 months of age [12 months after enrollment (age 18 months)]
Change in erythrocyte essential fatty acid (EFA) concentration (measured from a subsample of 400 participants) [12 months after enrollment (age 18 months)]
Neuro-behavioral development (timing of acquisition of the certain skills and more comprehensive analysis at the age of 18 months) [Limited assessment every 4 weeks during the 12 months supplementation, more comprehensive at age 18 months]
Incidence of all adverse events during the study period [12 months after enrollment (age 18 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

167 Days to 197 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Signed informed consent from at least one guardian
Age 5.50 months to 6.49 months
Availability during the period of the study.
Permanent resident of Mangochi District Hospital or Namwera Health Centre catchment area

Exclusion Criteria:

Weight for length Z score (WLZ) < -2.0
Presence of oedema
Severe anaemia (Hb<50 g / l)
Severe illness warranting hospital referral
History of allergy towards peanut
History of anaphylaxis or serious allergic reaction to any substance, requiring emergency medical care
Concurrent participation in any other clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Malawi, College of Medicine	Mangochi		Malawi

Sponsors and Collaborators

Tampere University
University of Malawi College of Medicine
University of California, Davis
Bill and Melinda Gates Foundation

Investigators

Principal Investigator: Per Ashorn, MD, PhD, University of Tampere Medical School
Principal Investigator: Kenneth Maleta, MBBS, PhD, University of Malawi College of Medicine