Gfree - For Improved Blood Sugar and Reduced Inflammation.

GFREE - A Study for Improved Blood Sugar Levels, Reduced Inflammation and for Increasing Knowledge of the Connection Between Diabetes and COVID-19.

The goal of this clinical trial is to reduce inflammation and improve glycemic control in healthy volunteers, parents, as well as children, adolescents and adults with or without diabetes. The main questions it aims to answer are: • does a reduction wheat gluten improve glycemic control and/or inflammatory biomarkers • does a reduction in certain amino acids (which is most common in wheat gluten) improve glycemic control and/or inflammatory biomarkers • can we identify individuals with an inflammatory response, which leads to poor glycemic control. Participants will eat gluten-free products as well as similar products containing gluten. They will also eat gluten together with probiotics to see if an effect of gluten can be reduced. Researchers will compare everyone with themselves (cross-over design) and if possible individuals with and without diabetes.

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Celiac Disease; Metabolic Disease; Autoimmunity
• Intervention / Treatment: Dietary supplement: gluten-free; Dietary supplement: gluten; Dietary supplement: probiotic

Detailed Description

BACKGROUND AND PURPOSE Many diseases, which are common in high-income countries, have an inflammatory component. In the world's rich countries, about 10% of the population will be diagnosed with a traditional inflammatory autoimmune disease during their lifetime. In an autoimmune disease, the body produces auto-antibodies against the body's own protein and the immune system destroys the body's own tissues. There are hundreds of different types of autoimmune diseases where some of the most common are; celiac disease (gluten intolerance), psoriasis, type 1 diabetes (T1D), multiple sclerosis, rheumatic diseases or thyroid diseases. Diseases such as cardiovascular disease, type 2 diabetes (T2D) and Alzheimer's disease are now also considered to have inflammatory components, and so-called auto-antibodies have been identified that indicate autoimmunity also in these diseases. Autoantibodies have also been identified in COVID-19 patients.

To try to understand the biology behind autoimmunity and inflammatory disease, the investigators have analyzed the entire genome of patients with celiac disease as a model for autoimmunity. Celiac disease is a good so-called model disease for autoimmunity because the autoimmune reaction can be switched on and off with the help of gluten in the diet. With a strict gluten-free diet, virtually all signs of illness disappear and the inflammation ceases. The results from our whole genome analysis showed that genes involved in amino acid signaling were important for disease development and pointed to associations between celiac disease, T2D and anorexia. These results were somewhat surprising and the investigators began to look at the role of nutritional signaling and amino acids in inflammatory processes further.

The purpose of this study is to test whether a reduction in certain amino acids (which is most common in wheat gluten) can improve glycemic control in healthy volunteers, parents, as well as children, adolescents and adults with diabetes and whether levels of inflammatory amino acids may be one of the factors behind the link between diabetes and severe COVID-19 infection.

The participants will, for 4 weeks, eat one week as usual, eat one week wheat gluten-free, one week wheat gluten and one week with gluten and probiotics. The participants will be provided with continuous glucose monitors and activity-tracking bracelets. The investigators will analyze the efficiency of glucose uptake using continuous glucose monitors (CGM). During these four weeks, the research subjects will be admitted for 4 clinical visits (baseline, after 1 week, 2 weeks, 3 weeks) where blood samples will be taken. Also, during these weeks the participant will take capillary blood samples, faeces, urine, buccal swabs and saliva at home and fill out a questionnaire based on diet and risk factors for diabetes and questions about COVID-19.

Total number of participants: 60 Sampling occasions per participant: 15 Follow-up period per participant: 4 weeks Number of years for inclusion: 2 years (20221201-20241201)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Åsa Torinsson Naluai, PhD; Phone Number: +46768979149; Email: asa.torinsson.naluai@gu.se
• Study Contact Backup: Name: Katarina Ejeskär Ejeskär, PhD; Email: Katarina.Ejeskar@his.se

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Not yet recruiting
    • Sahlgrenska University Hospital
    • Contact: Åsa Torinsson Naluai, PhD; Phone Number: +46768979149; Email: asa@clingen.gu.se
    • Principal Investigator: Åsa Torinsson Naluai, PhD
  • Skövde, Sweden
    • Recruiting
    • University of Skövde
    • Contact: Katarina Ejeskär, PhD; Email: Katarina.Ejeskar@his.se
    • Principal Investigator: Katarina Ejeskär, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

- none

Exclusion Criteria:

- A diagnosis of celiac disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gluten-free; The study participants will start the gluten-free diet and be asked to exchange any products they normally buy with similar products. Three days in the week they will eat a meal with gluten free pasta. Two to six hours after the meal they will take samples at home and store until they return to the clinic.	Dietary supplement: gluten-free; see info in arm description
Active Comparator: gluten; The study participants will continue the gluten-free diet and be asked to exchange any products they normally buy with similar products. Three days however, in the week they will eat a meal with regular gluten containing pasta. Two to six hours after the meal they will take samples at home and store until they return to the clinic.	Dietary supplement: gluten-free; see info in arm description; Dietary supplement: gluten; see info in arm description
Active Comparator: probiotic; The study participants will continue the gluten-free diet and be asked to exchange any products they normally buy with similar products. During the week they will also take probiotic (Probion, Active) every morning and every evening. Three days however, in the week they will eat a meal with regular gluten containing pasta. Two to six hours after the meal they will take samples at home and store until they return to the clinic.	Dietary supplement: gluten-free; see info in arm description; Dietary supplement: probiotic; see info in arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stabilizing of blood sugar levels	Continuous glucose monitoring (CGM) data will be analysed together with activity level data, lower glucose peaks after a meal, adjusted for activity level.	0 days to 4 weeks
Amino acid metabolism	Lowering of the aminoacid proline	0 days to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Lipids	LDL, improved apolipoprotein B (APOB)	0 days to 4 weeks
Glutathione S Transferases	Relative Glutathione S Transferases expression levels	0 days to 4 weeks
Fibrinogen	Relative Fibrinogen expression levels	0 days to 4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
multiomics explorative analyses	Genomics, transcriptomics2, metabolomics and proteomics analyses are planned	0 days to 4 weeks

Collaborators and Investigators

• Sponsor: Göteborg University
• Collaborators: Sahlgrenska University Hospital, Sweden; University of Skövde; Ekhaga foundation
• Investigators: Principal Investigator: Åsa Torinsson Naluai, PhD, Göteborg University; Study Director: Katarina Ejeskär, PhD, University of Skövde

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: June 7, 2023
• First Posted (Actual): June 8, 2023

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: probiotics; diet; gluten
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Inflammation; Celiac Disease; Metabolic Diseases
• Other Study ID Numbers: GFREE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan at the moment but the aim is to share data as much as possible.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No