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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Non-celiac Wheat Sensitivity

Intervention / Treatment
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* Other: Lactose breath test
* Other: DBPC cow's milk protein challenge


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Lactose breath test|Lactose breath test in NCWS patients with symptoms related to milk and/or milk derivates ingestion.|
|Other: DBPC cow's milk protein challenge|DBPC cow's milk protein challenge in NCWS patients with symptoms related to milk and/or milk derivates ingestion.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | January 2017 to December 2017 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactose intolerance and CMPA in NCWS patients | Frequency of lactose intolerance and CMPA in NCWS patients | January 2017 to December 2017 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-celiac wheat sensitivity, lactose intolerance, cow's milk protein allergy