Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight

Obesity Clinical Trial

— NAMI  

Official title:

Nutrition, Allergy, Mucosal Immunology and Intestinal Microbiota (NAMI): Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00167700
• Other study ID #: 15214
• Status: Recruiting
• Phase: N/A
• First received: September 11, 2005
• Last updated: October 3, 2012
• Start date: February 1997
• Est. completion date: December 2015

Study information

• Verified date: September 2012
• Source: University of Turku
• Contact: Johanna Hvitfelt-Koskelainen, RN
• Phone: +358 2 313 0000
• Email: Johanna.Hvitfelt-Koskelainen[@]tyks.fi
• Is FDA regulated: No
• Health authority: Finland: Ministry of Social Affairs and Health
• Study type: Interventional

Clinical Trial Summary

Combined programme: Nutrition, Allergy, Mucosal immunology and Intestinal microbiota (NAMI) was created with the objective to reverse the rising trend of chronic inflammatory diseases, such as allergic disease and obesity, by control of the internal and external environments of the infant. To approach this problem, the project aims to characterize

• how immunology is regulated during pregnancy and early infancy,

• how the immune interaction between mother and child is influenced by nutritional and microbial factors, and

• how the regulation is related to disease risk.

Description:

While allergic diseases comprise the most common chronic disease in childhood, obesity is the most prevalent nutritional disorder among children throughout the world. In Europe, an estimated 20% of children and adolescents are overweight with one-third of these being considered obese. Moreover, escalation of these problems is expected in the future, since the velocity of propagation is highest in children. Although genetic factors can determine the propensity of an individual to become allergic or obese, these unlikely explain the recent and progressive worldwide increases in incidence. Rather, it would appear that the environmental changes more directly shape the risk during a critical period of life when the scene is set for the consolidation of the immune responder type. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, heritable changes in gene expression occurring without alterations in the DNA sequences.

Specifically current research interest is directed towards health promotion and reducing the risk of disease evaluating the probiotic effects with specific foods and nutrients, and assessing their interactions in optimal combination and food matrix. For this purpose a series of interventions studies evaluate the both the optimal timing of probiotic intervention and the optimal mode of administration.

Sections:

Prenatal

RCT 2 Randomized, parallel-design clinical trial of 3 groups. Pregnant women (n=256) from families with at least one member having an allergic disease have been recruited from maternal welfare clinics and randomly assigned to control group or one of the intervention groups. Mothers in the dietary intervention groups received dietary counselling with specific attention to the quality and quantity of fat in the diet. To promote the achievement of current dietary recommendations, mothers have been provided with foods which have a favourable fat composition (e.g. spreads). The subjects in the intervention groups have been further randomized (double-blind randomization) to receive either placebo or a probiotic preparation, 1010 cfu of both Lactobacillus rhamnosus GG and Bifidobacterium lactis and controls received placebo in a single-blind manner. Dietary food products and probiotic supplementation have been continued from the 1st trimester of pregnancy until the end of exclusive breast feeding, maximum of 6 months.

Perinatal

RCT 1 Randomized double-blind, placebo-controlled study of 2 groups. Pregnant women (n=159) have been randomized into one of the study groups 2-4 weeks before term to receive placebo (microcrystalline cellulose) or probiotic Lactobacillus rhamnosus GG (ATCC 53103; 1010 cfu). After delivery probiotics/ placebo were administered orally to the infants for 6 months. General information to prevent allergy has been given in written form to all: to breast-feed for at least 4-6 months; to begin solid foods at 4-6 months; no smoking by caretakers.

RCT 3 Randomized double-blind, placebo-controlled clinical trial of 3 groups. Pregnant women (n=241) with a history of atopic diseases have been assigned to one of the treatment groups: to receive for 2 months before delivery and for 2 months thereafter, when they are breast-feeding, either placebo or Lactobacillus rhamnosus and Bifidobacterium longum or Lactobacillus paracasei and Bifidobacterium longum.

Postnatal

RCT 4 Randomized double-blind, placebo-controlled study of 3 groups. Neonates (n=94) fulfilling the following criteria: gestational age at birth between 32nd and 36th weeks, weight over 1500 g and no congenital defects of gastrointestinal system or other defects that prevent enteral nutrition, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) or a prebiotic preparation (a mixture of Polydextrose and Galacto-oligosaccharideOS in a 1:1 ratio). The treatment continues for 2 months.

RCT 5 Randomized double-blind, placebo-controlled clinical trial of 2 groups. 2-6 weeks old formula- and breast-fed colic infants (n=30), who cry without medical cause for 3h/d, for 3days/week, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) for 4 weeks. Formula-fed infants receive extensively hydrolysed formula and mothers of breast-fed infants avoid cow's milk in their diet.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pregnant women from families with at least one family member having an allergic disease

Exclusion Criteria:

• Women presenting severe immunological or other chronic diseases (rheumatoid arthritis, diabetes, inflammatory bowel disease, thyroid diseases, malignancies etc.)

• Women who cannot be expected to comply with treatment

• Women currently participating or having participated in other clinical trial during the last 2 months prior to the beginning of the intervention.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Allergic Disease
• Immunology
• Obesity

Intervention

Behavioral:
• Dietary counselling and placebo
Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Placebo capsules.
• Dietary counselling and probiotics
Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Probiotics

Dietary Supplement:
• Placebo capsules
Placebo capsules
• Probiotics

• Prebiotics

Locations

Country	Name	City	State
Finland	Turku University Central Hospital	Turku

Sponsors (2)

Lead Sponsor	Collaborator
University of Turku	Academy of Finland

Country where clinical trial is conducted

Finland, 

References & Publications (14)

Aaltonen J, Ojala T, Laitinen K, Poussa T, Ozanne S, Isolauri E. Impact of maternal diet during pregnancy and breastfeeding on infant metabolic programming: a prospective randomized controlled study. Eur J Clin Nutr. 2011 Jan;65(1):10-9. doi: 10.1038/ejcn — View Citation

Collado MC, Isolauri E, Laitinen K, Salminen S. Effect of mother's weight on infant's microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr. 2010 Nov;92(5):1023-3 — View Citation

Collado MC, Laitinen K, Salminen S, Isolauri E. Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk. Pediatr Res. 2012 Jul;72(1):77-85. doi: 10.1038/pr.2012.42. Epub 2012 Mar 27. — View Citation

Hoppu U, Isolauri E, Laakso P, Matomäki J, Laitinen K. Probiotics and dietary counselling targeting maternal dietary fat intake modifies breast milk fatty acids and cytokines. Eur J Nutr. 2012 Mar;51(2):211-9. doi: 10.1007/s00394-011-0209-0. Epub 2011 May — View Citation

Ilmonen J, Isolauri E, Poussa T, Laitinen K. Impact of dietary counselling and probiotic intervention on maternal anthropometric measurements during and after pregnancy: a randomized placebo-controlled trial. Clin Nutr. 2011 Apr;30(2):156-64. doi: 10.1016 — View Citation

Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001 Apr 7;357(9262):1076-9. — View Citation

Kalliomäki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet. 2003 May 31;361(9372):1869-71. — View Citation

Laiho K, Lampi AM, Hamalainen M, Moilanen E, Piironen V, Arvola T, Syrjanen S, Isolauri E. Breast milk fatty acids, eicosanoids, and cytokines in mothers with and without allergic disease. Pediatr Res. 2003 Apr;53(4):642-7. Epub 2003 Jan 29. — View Citation

Laitinen K, Kalliomäki M, Poussa T, Lagström H, Isolauri E. Evaluation of diet and growth in children with and without atopic eczema: follow-up study from birth to 4 years. Br J Nutr. 2005 Oct;94(4):565-74. — View Citation

Laitinen K, Poussa T, Isolauri E; Nutrition, Allergy, Mucosal Immunology and Intestinal Microbiota Group. Probiotics and dietary counselling contribute to glucose regulation during and after pregnancy: a randomised controlled trial. Br J Nutr. 2009 Jun;10 — View Citation

Luoto R, Laitinen K, Nermes M, Isolauri E. Impact of maternal probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration: a prospective, randomized, placebo-controlled study. Early Hum Dev. 2012 Jun;88(6):339-44. doi — View Citation

Luoto R, Laitinen K, Nermes M, Isolauri E. Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. Br J Nutr. 2010 Jun;103(12):1792-9. doi: 10.1017/S00 — View Citation

Niinivirta K, Isolauri E, Laakso P, Linderborg K, Laitinen K. Dietary counseling to improve fat quality during pregnancy alters maternal fat intake and infant essential fatty acid status. J Nutr. 2011 Jul;141(7):1281-5. doi: 10.3945/jn.110.137083. Epub 20 — View Citation

Ojala T, Aaltonen J, Siira S, Jalonen J, Ekholm E, Ekblad U, Laitinen K. Fetal cardiac sympathetic activation is linked with maternal body mass index. Early Hum Dev. 2009 Sep;85(9):557-60. doi: 10.1016/j.earlhumdev.2009.05.009. Epub 2009 Jun 12. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with allergic disease		Up to 13 years	No
Primary	Weight gain		Up to 13 years	No
Primary	Number of patients with chronic inflammatory disease		Up to 13 years	No
Secondary	Innate immune gene expression patterns		Up to 13 years	No
Secondary	Microbiota composition	Amount of bacterial cells (per gram of faeces of mothers and infants as well as of breast milk) is measured using multiple methods, i.e. pyrosequencing, HIT-CHIP, qPCR, FISH and DGGE.		No
Secondary	Plasma glucose		Up to 13 years	No
Secondary	Cytokines in peripheral blood		Up to 13 years	No
Secondary	Cytokine profile in breast milk		Up to 13 years	No
Secondary	Cytokine profile in peripheral blood mononuclear cells (PBMC)		Up to 13 years	No
Secondary	GHbA1c		Up to 13 years	No
Secondary	Fatty acids		Up to 13 years	No
Secondary	Lipoproteins		Up to 13 years	No
Secondary	Intakes of foods and nutrients		Up to 13 years	No
Secondary	Blood pressure		Up to 13 years	No
Secondary	Leukotrienes in peripheral blood		Up to 13 years	No
Secondary	Adipokines		Up to 13 years	No
Secondary	Amount of crying in minutes	Crying minutes per day	Up to 1 year	No
Secondary	Number of patients with functional gastrointestinal disorders		Up to 13 years	No
Secondary	Incidence of viral infections		Up to 13 years	No

External Links

•   The home page of the research group (only partly in English)