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

Primary Purpose

Allergic Disease, Obesity, Immunology

Status
Unknown status
Phase
Not Applicable
Locations
Finland
Study Type
Interventional
Intervention
Dietary counselling and placebo
Dietary counselling and probiotics
Placebo capsules
Probiotics
Prebiotics
Sponsored by
University of Turku
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Allergic Disease focused on measuring atopic disease, probiotics, gut microbiota, allergy, nutrition, growth, allergic rhinitis, atopic sensitization, risk-markers of life-style related diseases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Turku University Central HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

No Intervention

Arm Label

Probiotics

Probiotics + Dietary counseling

Dietary counseling + placebo

Prebiotics

Placebo

Control

Arm Description

Outcomes

Primary Outcome Measures

Number of participants with allergic disease
Weight gain
Number of patients with chronic inflammatory disease

Secondary Outcome Measures

Innate immune gene expression patterns
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.
Plasma glucose
Cytokines in peripheral blood
Cytokine profile in breast milk
Cytokine profile in peripheral blood mononuclear cells (PBMC)
GHbA1c
Fatty acids
Lipoproteins
Intakes of foods and nutrients
Blood pressure
Leukotrienes in peripheral blood
Adipokines
Amount of crying in minutes
Crying minutes per day
Number of patients with functional gastrointestinal disorders
Incidence of viral infections

Full Information

First Posted
September 11, 2005
Last Updated
October 3, 2012
Sponsor
University of Turku
Collaborators
Academy of Finland
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1. Study Identification

Unique Protocol Identification Number
NCT00167700
Brief Title
Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Unknown status
Study Start Date
February 1997 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 2015 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
University of Turku
Collaborators
Academy of Finland

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allergic Disease, Obesity, Immunology
Keywords
atopic disease, probiotics, gut microbiota, allergy, nutrition, growth, allergic rhinitis, atopic sensitization, risk-markers of life-style related diseases

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
800 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Probiotics
Arm Type
Experimental
Arm Title
Probiotics + Dietary counseling
Arm Type
Experimental
Arm Title
Dietary counseling + placebo
Arm Type
Experimental
Arm Title
Prebiotics
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Control
Arm Type
No Intervention
Intervention Type
Behavioral
Intervention Name(s)
Dietary counselling and placebo
Intervention Description
Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Placebo capsules.
Intervention Type
Behavioral
Intervention Name(s)
Dietary counselling and probiotics
Intervention Description
Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Probiotics
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo capsules
Intervention Description
Placebo capsules
Intervention Type
Dietary Supplement
Intervention Name(s)
Probiotics
Intervention Type
Dietary Supplement
Intervention Name(s)
Prebiotics
Primary Outcome Measure Information:
Title
Number of participants with allergic disease
Time Frame
Up to 13 years
Title
Weight gain
Time Frame
Up to 13 years
Title
Number of patients with chronic inflammatory disease
Time Frame
Up to 13 years
Secondary Outcome Measure Information:
Title
Innate immune gene expression patterns
Time Frame
Up to 13 years
Title
Microbiota composition
Description
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.
Title
Plasma glucose
Time Frame
Up to 13 years
Title
Cytokines in peripheral blood
Time Frame
Up to 13 years
Title
Cytokine profile in breast milk
Time Frame
Up to 13 years
Title
Cytokine profile in peripheral blood mononuclear cells (PBMC)
Time Frame
Up to 13 years
Title
GHbA1c
Time Frame
Up to 13 years
Title
Fatty acids
Time Frame
Up to 13 years
Title
Lipoproteins
Time Frame
Up to 13 years
Title
Intakes of foods and nutrients
Time Frame
Up to 13 years
Title
Blood pressure
Time Frame
Up to 13 years
Title
Leukotrienes in peripheral blood
Time Frame
Up to 13 years
Title
Adipokines
Time Frame
Up to 13 years
Title
Amount of crying in minutes
Description
Crying minutes per day
Time Frame
Up to 1 year
Title
Number of patients with functional gastrointestinal disorders
Time Frame
Up to 13 years
Title
Incidence of viral infections
Time Frame
Up to 13 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Johanna Hvitfelt-Koskelainen, RN
Phone
+358 2 313 0000
Ext
1463
Email
Johanna.Hvitfelt-Koskelainen@tyks.fi
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erika Isolauri, MD, PhD
Organizational Affiliation
University of Turku
Official's Role
Study Director
Facility Information:
Facility Name
Turku University Central Hospital
City
Turku
ZIP/Postal Code
20520
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erika Isolauri, MD, PhD
Phone
+358 2 313 0000
Ext
2433
Email
erika.isolauri@utu.fi
First Name & Middle Initial & Last Name & Degree
Erika Isolauri, MD, PhD
First Name & Middle Initial & Last Name & Degree
Seppo Salminen, PhD
First Name & Middle Initial & Last Name & Degree
Kirsi Laitinen, PhD
First Name & Middle Initial & Last Name & Degree
Marko Kalliomäki, MD, PhD
First Name & Middle Initial & Last Name & Degree
Samuli Rautava, MD, PhD
First Name & Middle Initial & Last Name & Degree
Minna-Maija Grönlund, MD, PhD
First Name & Middle Initial & Last Name & Degree
Merja Nermes, MD, PhD
First Name & Middle Initial & Last Name & Degree
Maria Carmen Collado, PhD
First Name & Middle Initial & Last Name & Degree
Ulla Hoppu, PhD
First Name & Middle Initial & Last Name & Degree
Raakel Luoto, MD, PhD
First Name & Middle Initial & Last Name & Degree
Jonna Normia, MD, PhD

12. IPD Sharing Statement

Citations:
PubMed Identifier
11297958
Citation
Kalliomaki 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. doi: 10.1016/S0140-6736(00)04259-8.
Results Reference
result
PubMed Identifier
12788576
Citation
Kalliomaki 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. doi: 10.1016/S0140-6736(03)13490-3.
Results Reference
result
PubMed Identifier
12612204
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. doi: 10.1203/01.PDR.0000055778.58807.C8. Epub 2003 Jan 29.
Results Reference
result
PubMed Identifier
16197582
Citation
Laitinen K, Kalliomaki M, Poussa T, Lagstrom 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. doi: 10.1079/bjn20051503.
Results Reference
result
PubMed Identifier
22453296
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.
Results Reference
result
PubMed Identifier
19017418
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;101(11):1679-87. doi: 10.1017/S0007114508111461. Epub 2008 Nov 19.
Results Reference
result
PubMed Identifier
21626296
Citation
Hoppu U, Isolauri E, Laakso P, Matomaki 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 31.
Results Reference
result
PubMed Identifier
21593355
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 2011 May 18.
Results Reference
result
PubMed Identifier
20970896
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/j.clnu.2010.09.009.
Results Reference
result
PubMed Identifier
21945174
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: 10.1016/j.earlhumdev.2011.09.006. Epub 2011 Sep 25.
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PubMed Identifier
19524376
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.
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PubMed Identifier
20128938
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/S0007114509993898. Epub 2010 Feb 4.
Results Reference
result
PubMed Identifier
20844065
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):1023-30. doi: 10.3945/ajcn.2010.29877. Epub 2010 Sep 15.
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result
PubMed Identifier
20948557
Citation
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.2010.225. Epub 2010 Oct 13.
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PubMed Identifier
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Citation
Davidson SJ, Barrett HL, Price SA, Callaway LK, Dekker Nitert M. Probiotics for preventing gestational diabetes. Cochrane Database Syst Rev. 2021 Apr 19;4(4):CD009951. doi: 10.1002/14651858.CD009951.pub3.
Results Reference
derived
PubMed Identifier
27478897
Citation
Partty A, Kalliomaki M, Salminen S, Isolauri E. Infantile Colic Is Associated With Low-grade Systemic Inflammation. J Pediatr Gastroenterol Nutr. 2017 May;64(5):691-695. doi: 10.1097/MPG.0000000000001340.
Results Reference
derived
PubMed Identifier
26151493
Citation
Partty A, Lehtonen L, Kalliomaki M, Salminen S, Isolauri E. Probiotic Lactobacillus rhamnosus GG therapy and microbiological programming in infantile colic: a randomized, controlled trial. Pediatr Res. 2015 Oct;78(4):470-5. doi: 10.1038/pr.2015.127. Epub 2015 Jul 7.
Results Reference
derived
PubMed Identifier
24131826
Citation
Luoto R, Ruuskanen O, Waris M, Kalliomaki M, Salminen S, Isolauri E. Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2014 Feb;133(2):405-13. doi: 10.1016/j.jaci.2013.08.020. Epub 2013 Oct 13.
Results Reference
derived
PubMed Identifier
23915796
Citation
Partty A, Luoto R, Kalliomaki M, Salminen S, Isolauri E. Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial. J Pediatr. 2013 Nov;163(5):1272-7.e1-2. doi: 10.1016/j.jpeds.2013.05.035. Epub 2013 Jul 31.
Results Reference
derived
PubMed Identifier
22836031
Citation
Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012 Sep;96(3):544-51. doi: 10.3945/ajcn.112.037382. Epub 2012 Jul 25.
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derived
PubMed Identifier
22228076
Citation
Grzeskowiak L, Collado MC, Mangani C, Maleta K, Laitinen K, Ashorn P, Isolauri E, Salminen S. Distinct gut microbiota in southeastern African and northern European infants. J Pediatr Gastroenterol Nutr. 2012 Jun;54(6):812-6. doi: 10.1097/MPG.0b013e318249039c.
Results Reference
derived
PubMed Identifier
21979491
Citation
Grzeskowiak L, Gronlund MM, Beckmann C, Salminen S, von Berg A, Isolauri E. The impact of perinatal probiotic intervention on gut microbiota: double-blind placebo-controlled trials in Finland and Germany. Anaerobe. 2012 Feb;18(1):7-13. doi: 10.1016/j.anaerobe.2011.09.006. Epub 2011 Sep 29.
Results Reference
derived
PubMed Identifier
18025796
Citation
Huurre A, Kalliomaki M, Rautava S, Rinne M, Salminen S, Isolauri E. Mode of delivery - effects on gut microbiota and humoral immunity. Neonatology. 2008;93(4):236-40. doi: 10.1159/000111102. Epub 2007 Nov 16.
Results Reference
derived

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

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