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CompletedNCT03008252Updated Oct 8, 2020

Lactose Intolerance and Cow's Milk Protein Allergy in Non-celiac Wheat Sensitivity Patients

An observational study in Non-celiac Wheat Sensitivity, sponsored by University of Palermo. Completed at 2 sites in Italy. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2020-10-08.

Sponsored by University of Palermo · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
300
Ages
18 Years to 65 Years
Sex
All
01

Study summary

In the last few years a new clinical entity has emerged which includes patients who consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy. This clinical condition has been named non-celiac gluten sensitivity (NCGS), although in a recent article, the researchers suggested the term "non-celiac wheat sensitivity" (NCWS), because it is not known to date what component of wheat actually causes the symptoms. The clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and extra-intestinal or systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Lactose intolerance and cow's milk protein allergy (CMPA) are two medical conditions with a very high prevalence in the general population, and there is a large overlap between NCWS symptoms and lactose intolerance and CMPA symptoms. Therefore, the aims of the present study are to investigate 1) the prevalence of positive lactose breath test and DBPC cow's milk protein challenge in NCWS patients with self-reported gastrointestinal symptoms related to milk and/or milk derivates ingestion, 2) the clinical, serological, and histological characteristics of NCWS patients with lactose intolerance and CMPA in comparison to NCWS patients without lactose intolerance and CMPA.

Read the detailed description

In the last few years, a new clinical entity has emerged which includes patients who consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy. This clinical condition has been named non-celiac gluten sensitivity (NCGS), although in a recent article, the researchers suggested the term "non-celiac wheat sensitivity" (NCWS), because it is not known to date what component of wheat actually causes the symptoms. Other areas of doubt in NCWS regard its pathogenesis, while some papers reported intestinal immunologic activation, others linked NCWS to the dietary short chain carbohydrate (fermentable oligo-di-monosaccharides and polyols, FODMAPs) load. The researchers recently demonstrated that higher proportions of patients with NCWS develop autoimmune disorders, are antinuclear antibodies (ANA) positive, and show DQ2/DQ8 haplotypes compared with patients with irritable bowel syndrome (IBS), supporting an immunologic involvement in NCWS. The clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and extra-intestinal or systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Lactose intolerance and cow's milk protein allergy (CMPA) are two conditions with a very high prevalence in the general population and there is a large overlap between NCWS and lactose intolerance and CMPA symptoms. Therefore, the aims of the present study are to investigate 1) the prevalence of positive lactose breath test and DBPC cow's milk protein challenge in NCWS patients with self-reported gastrointestinal and extra-intestinal symptoms related to milk and/or milk derivates ingestion, 2) the clinical, serological, and histological characteristics of NCWS patients with lactose intolerance and CMPA in comparison to NCWS patients without lactose intolerance and CMPA.

02

Conditions studied

  • Non-celiac Wheat Sensitivity

Keywords

  • Non-celiac wheat sensitivity
  • lactose intolerance
  • cow's milk protein allergy
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Probability sample

Study population

The researchers prospectively will survey adult patients with functional gastroenterological symptoms (Rome III criteria) and a definitive diagnosis of NCWS, referred at the Department of Internal Medicine at the University Hospital of Palermo, Italy, and at the Department of Internal Medicine of the Hospital of Sciacca, Agrigento, Italy, between January 2017 and January 2019, comparing the characteristics of the ones suffering from lactose intolerance and CMPA with those who do not suffer from lactose intolerance and CMPA.

Eligibility criteria

Inclusion Criteria:

All the NCWS patients will meet the recently proposed criteria:

  • negative serum anti-tissue transglutaminase and antiendomysium (EmA) IgA and IgG antibodies
  • absence of intestinal villous atrophy
  • IgE-mediated immunoallergy tests negative to wheat and cow's milk protein (skin prick tests and/or serum specific IgE detection).

Adjunctive criteria adopted in our patients will be:

  • resolution of the gastrointestinal and extra-intestinal symptoms on a standard elimination diet, without wheat, cow's milk, egg, tomato, chocolate, or other food(s) causing self-reported symptoms
  • symptom reappearance on double-blind placebo-controlled (DBPC) wheat challenge, performed as described previously.

Exclusion Criteria:

Exclusion criteria will be:

  • age \<18 years
  • positive EmA in the culture medium of the duodenal biopsies, even if the villi to crypts ratio in the duodenal mucosa was normal
  • self-exclusion of wheat from the diet and refusal to reintroduce it before entering the study
  • other organic cutaneous and/or gastrointestinal diseases
  • concomitant treatment with steroids and/or antihistamines.

Lactose intolerance and CMPA will be diagnosed, in patients with self-reported gastrointestinal and extra-intestinal symptoms related to milk and/or milk derivates ingestion, using lactose breath test and DBPC cow's milk protein challenge, respectively.

04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
300 participants (actual)
Patient registry
No

Interventions

  • OtherLactose breath test

    Lactose breath test in NCWS patients with symptoms related to milk and/or milk derivates ingestion.

  • OtherDBPC cow's milk protein challenge

    DBPC cow's milk protein challenge in NCWS patients with symptoms related to milk and/or milk derivates ingestion.

05

What researchers measure

Primary outcomes

  1. Positive lactose breath test and DBPC cow's milk protein challenge in NCWS patients self-reporting symptoms related to milk and/or milk derivates ingestion.

    Prevalence of positive lactose breath test and DBPC cow's milk protein challenge in NCWS patients with self-reported gastrointestinal and extra-intestinal symptoms related to milk and/or milk derivates ingestion.

    Time frame: January 2017 to December 2017

Secondary outcomes

  1. Lactose intolerance and CMPA in NCWS patients

    Frequency of lactose intolerance and CMPA in NCWS patients

    Time frame: January 2017 to December 2017

06

Study locations

2 sites
  • Internal Medicine Department of the Hospital of Sciacca (Agrigento)
    Sciacca, Agrigento 92019, Italy
  • Internal Medicine Department of the University Hospital of Palermo
    Palermo, 90127, Italy
07

References and documents

Publications

  • Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012 Dec;107(12):1898-906; quiz 1907. doi: 10.1038/ajg.2012.236. Epub 2012 Jul 24. PubMed 22825366 ↗
  • Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr. 2014;33(1):39-54. doi: 10.1080/07315724.2014.869996. PubMed 24533607 ↗
  • Carroccio A, Rini G, Mansueto P. Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten sensitivity. Gastroenterology. 2014 Jan;146(1):320-1. doi: 10.1053/j.gastro.2013.08.061. Epub 2013 Nov 22. No abstract available. PubMed 24275240 ↗
  • Carroccio A, D'Alcamo A, Mansueto P. Nonceliac wheat sensitivity in the context of multiple food hypersensitivity: new data from confocal endomicroscopy. Gastroenterology. 2015 Mar;148(3):666-7. doi: 10.1053/j.gastro.2014.11.047. Epub 2015 Jan 24. No abstract available. PubMed 25625764 ↗
  • Carroccio A, Soresi M, D'Alcamo A, Sciume C, Iacono G, Geraci G, Brusca I, Seidita A, Adragna F, Carta M, Mansueto P. Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study. BMC Med. 2014 Nov 28;12:230. doi: 10.1186/s12916-014-0230-2. PubMed 25430806 ↗
  • Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Role of FODMAPs in Patients With Irritable Bowel Syndrome. Nutr Clin Pract. 2015 Oct;30(5):665-82. doi: 10.1177/0884533615569886. Epub 2015 Feb 18. PubMed 25694210 ↗
  • Carroccio A, Brusca I, Mansueto P, D'alcamo A, Barrale M, Soresi M, Seidita A, La Chiusa SM, Iacono G, Sprini D. A comparison between two different in vitro basophil activation tests for gluten- and cow's milk protein sensitivity in irritable bowel syndrome (IBS)-like patients. Clin Chem Lab Med. 2013 Jun;51(6):1257-63. doi: 10.1515/cclm-2012-0609. PubMed 23183757 ↗
  • Carroccio A, Montalto G, Custro N, Notarbartolo A, Cavataio F, D'Amico D, Alabrese D, Iacono G. Evidence of very delayed clinical reactions to cow's milk in cow's milk-intolerant patients. Allergy. 2000 Jun;55(6):574-9. doi: 10.1034/j.1398-9995.2000.00417.x. PubMed 10858991 ↗
  • Carroccio A, Montalto G, Cavera G, Notarbatolo A. Lactose intolerance and self-reported milk intolerance: relationship with lactose maldigestion and nutrient intake. Lactase Deficiency Study Group. J Am Coll Nutr. 1998 Dec;17(6):631-6. doi: 10.1080/07315724.1998.10718813. PubMed 9853544 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03008252
Lead sponsor
University of Palermo
Responsible party
Pasquale Mansueto (MD, University of Palermo) — Principal investigator
First posted
Jan 2, 2017
Start date
Jan 1, 2017
Primary completion
Jul 1, 2017
Completion
Jun 1, 2020
Last update
Oct 8, 2020

Study contacts

Antonio Carroccio, PhD
study director · University of Palermo

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Oct 2020. You cannot join it, but the record below documents what was studied.

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