The Effect of a Gluten Free Diet on the Permeability of the Blood Brain Barrier in Patients With CIS

NCT03451955 | Completed

• 1 other identifier: H-17019986
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 2

Brief Summary

Disruption of the blood brain barrier (BBB) is associated with inflammatory conditions of the central nervous system (CNS). This clinical trial aims to investigate whether following a gluten-free diet (GFD) for six months can contribute to normalizing BBB permeability in patients with newly diagnosed clinically isolated syndrome (CIS) and multiple sclerosis (MS). Furthermore, the study seeks to identify possible effects of a GFD on markers of systemic as well as CNS inflammation. Lastly, gut permeability is measured in order to examine whether there are any correlations between the permeability of the gut and the BBB as well as the inflammatory state in the intestine and CNS. From a patient's view, potential positive effects of a GFD will be manifested through an alleviation of symptoms, improved quality of life and reduced risk of CIS progressing to MS. Evaluating a possible role of gluten in MS pathogenesis can contribute to directing future research and optimizing treatment protocols.

Conditions

Optic Neuritis; Multiple Sclerosis; Clinically Isolated Syndrome

Keywords

gluten; gluten free diet; blood brain barrier permeability; intestinal permeability; neuroinflammation; autoimmunity

Outcome Measures

Primary Outcomes (1)

• Permeability of the blood brain barrier

  Blood brain barrier permeability measured by contrast enhanced magnetic resonance imaging as well as concentration of pre-haptoglobin 2 in CSF

  Change from baseline at 6 months

Secondary Outcomes (9)

• Intestinal permeability

  Change from baseline at 6 months

• Intestinal absorption capacity

  Change from baseline at 6 months

• Counts of T cell subpopulations in peripheral blood and CSF

  Change from baseline at 6 months

• Macrophage activation in peripheral blood and CSF

  Change from baseline at 6 months

• Neuroinflammation

  Change from baseline at 6 months

Study Arms (2)

Intervention group

EXPERIMENTAL

Patients in the intervention group follow a gluten-free diet for six months.

Other: Gluten-free diet

Control group

NO INTERVENTION

Patients in the control group follow their usual diet for six months

Interventions

Gluten-free diet OTHER

Participants in the intervention group abstain from gluten for 6 months.

Intervention group

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult men and women ≥18 and ≤59 years of age
• Patients with newly diagnosed CIS or MS deemed physically and mentally able to participate in a study

You may not qualify if:

• More conflicting disorders in the same patient
• Pregnancy and lactating women and women planning pregnancy during the study period
• People with severe claustrophobia
• People with MR incompatible implants/ foreign objects, including implanted pacemakers, heart valve prostheses, prostheses in the middle ear, implanted devices (e.g. insulin pump), metal debris, e.g. metal splinters in the eyes, miscellaneous shunts and catheters, metal clips from operations
• Surgeries within the last 6 weeks
• Previous reactions to MR contrast agent, bronchial asthma or history of other allergies
• Elevated serum creatinine
• People already on a gluten restricted/ GFD

Sponsors & Collaborators

• University of Copenhagen: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (2)

University of Copenhagen

Copenhagen, Frederiksberg, 1958, Denmark

Location

Rigshopitalet

Glostrup Municipality, 2600, Denmark

Location

Related Publications (13)

• Cramer SP, Simonsen H, Frederiksen JL, Rostrup E, Larsson HB. Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI. Neuroimage Clin. 2013 Dec 10;4:182-9. doi: 10.1016/j.nicl.2013.12.001. eCollection 2014.

  PMID: 24371801 BACKGROUND

• Cramer SP, Modvig S, Simonsen HJ, Frederiksen JL, Larsson HB. Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis. Brain. 2015 Sep;138(Pt 9):2571-83. doi: 10.1093/brain/awv203. Epub 2015 Jul 17.

  PMID: 26187333 BACKGROUND

• Sorensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, Qin S, Rottman J, Sellebjerg F, Strieter RM, Frederiksen JL, Ransohoff RM. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest. 1999 Mar;103(6):807-15. doi: 10.1172/JCI5150.

  PMID: 10079101 BACKGROUND

• Andalib A, Doulabi H, Najafi M, Tazhibi M, Rezaie A. Expression of chemokine receptors on Th1/Th2 CD4+ lymphocytes in patients with multiple sclerosis. Iran J Immunol. 2011 Mar;8(1):1-10.

  PMID: 21427490 BACKGROUND

• Lammers KM, Lu R, Brownley J, Lu B, Gerard C, Thomas K, Rallabhandi P, Shea-Donohue T, Tamiz A, Alkan S, Netzel-Arnett S, Antalis T, Vogel SN, Fasano A. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology. 2008 Jul;135(1):194-204.e3. doi: 10.1053/j.gastro.2008.03.023. Epub 2008 Mar 21.

  PMID: 18485912 BACKGROUND

• Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S, Buzza MS, Antalis TM, Vogel SN, Zhao A, Yang S, Arrietta MC, Meddings JB, Fasano A. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16799-804. doi: 10.1073/pnas.0906773106. Epub 2009 Sep 15.

  PMID: 19805376 BACKGROUND

• Buscarinu MC, Cerasoli B, Annibali V, Policano C, Lionetto L, Capi M, Mechelli R, Romano S, Fornasiero A, Mattei G, Piras E, Angelini DF, Battistini L, Simmaco M, Umeton R, Salvetti M, Ristori G. Altered intestinal permeability in patients with relapsing-remitting multiple sclerosis: A pilot study. Mult Scler. 2017 Mar;23(3):442-446. doi: 10.1177/1352458516652498. Epub 2016 Jul 11.

  PMID: 27270497 BACKGROUND

• van Strien ME, Drukarch B, Bol JG, van der Valk P, van Horssen J, Gerritsen WH, Breve JJ, van Dam AM. Appearance of tissue transglutaminase in astrocytes in multiple sclerosis lesions: a role in cell adhesion and migration? Brain Pathol. 2011 Jan;21(1):44-54. doi: 10.1111/j.1750-3639.2010.00428.x. Epub 2010 Aug 20.

  PMID: 20731658 BACKGROUND

• van Strien ME, de Vries HE, Chrobok NL, Bol JGJM, Breve JJP, van der Pol SMP, Kooij G, van Buul JD, Karpuj M, Steinman L, Wilhelmus MM, Sestito C, Drukarch B, Van Dam AM. Tissue Transglutaminase contributes to experimental multiple sclerosis pathogenesis and clinical outcome by promoting macrophage migration. Brain Behav Immun. 2015 Nov;50:141-154. doi: 10.1016/j.bbi.2015.06.023. Epub 2015 Jun 29.

  PMID: 26133787 BACKGROUND

• Antvorskov JC, Josefsen K, Engkilde K, Funda DP, Buschard K. Dietary gluten and the development of type 1 diabetes. Diabetologia. 2014 Sep;57(9):1770-80. doi: 10.1007/s00125-014-3265-1. Epub 2014 May 29.

  PMID: 24871322 BACKGROUND

• Svensson J, Sildorf SM, Pipper CB, Kyvsgaard JN, Bojstrup J, Pociot FM, Mortensen HB, Buschard K. Potential beneficial effects of a gluten-free diet in newly diagnosed children with type 1 diabetes: a pilot study. Springerplus. 2016 Jul 7;5(1):994. doi: 10.1186/s40064-016-2641-3. eCollection 2016.

  PMID: 27398272 BACKGROUND

• Jelinkova L, Tuckova L, Cinova J, Flegelova Z, Tlaskalova-Hogenova H. Gliadin stimulates human monocytes to production of IL-8 and TNF-alpha through a mechanism involving NF-kappaB. FEBS Lett. 2004 Jul 30;571(1-3):81-5. doi: 10.1016/j.febslet.2004.06.057.

  PMID: 15280021 BACKGROUND

• Nouri M, Bredberg A, Westrom B, Lavasani S. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells. PLoS One. 2014 Sep 3;9(9):e106335. doi: 10.1371/journal.pone.0106335. eCollection 2014.

  PMID: 25184418 BACKGROUND

MeSH Terms

Conditions

Optic Neuritis; Multiple Sclerosis; Neuroinflammatory Diseases; Autoimmune Diseases

Interventions

Diet, Gluten-Free

Condition Hierarchy (Ancestors)

Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Immune System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Jens Rikardt Andersen

  University of Copenhagen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: September 22, 2017
• First Posted: March 2, 2018
• Study Start: January 19, 2018
• Primary Completion: June 7, 2022
• Study Completion: June 16, 2022
• Last Updated: December 28, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)