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

Non-celiac Wheat Sensitivity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03008252
• Other study ID #: ACPM12
• Status: Completed
• Start date: January 1, 2017
• Est. completion date: June 1, 2020

Study information

• Verified date: October 2020
• Source: University of Palermo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: June 1, 2020
• Est. primary completion date: July 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypersensitivity
• Lactose Intolerance
• Non-celiac Wheat Sensitivity

Intervention

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

Locations

Country	Name	City	State
Italy	Internal Medicine Department of the University Hospital of Palermo	Palermo
Italy	Internal Medicine Department of the Hospital of Sciacca (Agrigento)	Sciacca	Agrigento

Sponsors (1)

Lead Sponsor	Collaborator
University of Palermo

Country where clinical trial is conducted

Italy, 

References & Publications (9)

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 syndro — View Citation

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. — View Citation

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. A — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Carroccio A, Soresi M, D'Alcamo A, Sciumè 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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Lactose intolerance and CMPA in NCWS patients	Frequency of lactose intolerance and CMPA in NCWS patients	January 2017 to December 2017