Trial Outcomes & Findings for Assessment of Immune Activation and Tolerance in Celiac Disease During Gluten Challenge (NCT NCT03409796)
NCT ID: NCT03409796
Last Updated: 2022-05-24
Results Overview
Attenuation of the effects of gluten exposure was assessed by measuring the change from baseline in villous height (Vh) to crypt depth (Cd) ratio after 15 days of gluten challenge. Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CeD. Crypts were grooves between the villi that are often elongated in participants with CeD. A decreased Vh:Cd ratio indicates more extreme CeD disease symptoms. Baseline values was defined as the last observed value before the first dose of gluten.
COMPLETED
NA
16 participants
Baseline and Day 15
2022-05-24
Participant Flow
Participants took part in the study at 2 investigative sites in the Unites Stated from 24 April 2018 to 02 May 2019.
Participants diagnosed with celiac disease (CeD) were enrolled in a 1:1 ratio in one of the two treatment groups: 3 gram gluten per day or 10 gram gluten per day.
Participant milestones
| Measure |
Group A: Gluten 3 Gram
Gluten 3 gram, powder, orally, once daily up to 14 days.
|
Group B: Gluten 10 Gram
Gluten 10 gram, powder, orally, once daily up to 14 days.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
7
|
|
Overall Study
COMPLETED
|
7
|
6
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Group A: Gluten 3 Gram
Gluten 3 gram, powder, orally, once daily up to 14 days.
|
Group B: Gluten 10 Gram
Gluten 10 gram, powder, orally, once daily up to 14 days.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Other
|
0
|
1
|
Baseline Characteristics
Assessment of Immune Activation and Tolerance in Celiac Disease During Gluten Challenge
Baseline characteristics by cohort
| Measure |
Group A: Gluten 3 Gram
n=9 Participants
Gluten 3 gram, powder, orally, once daily up to 14 days.
|
Group B: Gluten 10 Gram
n=7 Participants
Gluten 10 gram, powder, orally, once daily up to 14 days.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44.2 years
STANDARD_DEVIATION 18.12 • n=5 Participants
|
46.0 years
STANDARD_DEVIATION 18.86 • n=7 Participants
|
45.0 years
STANDARD_DEVIATION 17.84 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Height
|
165.12 centimeter (cm)
STANDARD_DEVIATION 9.648 • n=5 Participants
|
169.76 centimeter (cm)
STANDARD_DEVIATION 8.074 • n=7 Participants
|
167.15 centimeter (cm)
STANDARD_DEVIATION 9.020 • n=5 Participants
|
|
Weight
|
75.23 kilogram (kg)
STANDARD_DEVIATION 17.183 • n=5 Participants
|
81.36 kilogram (kg)
STANDARD_DEVIATION 8.121 • n=7 Participants
|
77.91 kilogram (kg)
STANDARD_DEVIATION 13.918 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 15Population: The biomarker analysis set consisted of all participants had two endoscopic examinations with biopsies, one before and one after gluten challenge.
Attenuation of the effects of gluten exposure was assessed by measuring the change from baseline in villous height (Vh) to crypt depth (Cd) ratio after 15 days of gluten challenge. Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CeD. Crypts were grooves between the villi that are often elongated in participants with CeD. A decreased Vh:Cd ratio indicates more extreme CeD disease symptoms. Baseline values was defined as the last observed value before the first dose of gluten.
Outcome measures
| Measure |
Group A: Gluten 3 Gram
n=7 Participants
Gluten 3 gram, powder, orally, once daily up to 14 days.
|
Group B: Gluten 10 Gram
n=7 Participants
Gluten 10 gram, powder, orally, once daily up to 14 days.
|
|---|---|---|
|
Change From Baseline in Small Intestine Histology Based on Villous Height to Crypt Depth (Vh:Cd) Ratio
Baseline
|
2.10 ratio
Standard Deviation 0.697
|
2.30 ratio
Standard Deviation 0.893
|
|
Change From Baseline in Small Intestine Histology Based on Villous Height to Crypt Depth (Vh:Cd) Ratio
Change at Day 15
|
-0.06 ratio
Standard Deviation 0.516
|
-1.53 ratio
Standard Deviation 0.941
|
PRIMARY outcome
Timeframe: Baseline and Day 15Population: The biomarker analysis set consisted of all participants who had two endoscopic examinations with biopsies, one before and one after gluten challenge.
IELs are white blood cells (WBCs) interspersed between epithelial cells of the small and large intestine where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen or immune-induced pathology. Increased IELs count indicated more extreme CeD disease symptoms. Baseline values was defined as the last observed value before the first dose of gluten.
Outcome measures
| Measure |
Group A: Gluten 3 Gram
n=7 Participants
Gluten 3 gram, powder, orally, once daily up to 14 days.
|
Group B: Gluten 10 Gram
n=7 Participants
Gluten 10 gram, powder, orally, once daily up to 14 days.
|
|---|---|---|
|
Change From Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Counts
Baseline
|
26.74 IEL per 100 epithelial cells
Standard Deviation 15.861
|
26.68 IEL per 100 epithelial cells
Standard Deviation 8.248
|
|
Change From Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Counts
Change at Day 15
|
9.56 IEL per 100 epithelial cells
Standard Deviation 15.206
|
26.80 IEL per 100 epithelial cells
Standard Deviation 14.908
|
SECONDARY outcome
Timeframe: At Baseline, Days 6 and 15Population: The biomarker analysis set consisted of all participants who had two endoscopic examinations with biopsies, one before and one after gluten challenge.
Standard measures used for diagnosing CeD: Vh:CD ratio and IEL counts. T cell measurements taken before first dose of gluten were correlated with Baseline Vh:Cd ratio and IEL counts, and T cell measurements taken after first dose of gluten were correlated with Day 15 Vh:Cd ratio and IEL counts using Spearman correlation. Villi were small finger like projections that line small intestine, promote nutrient absorption and are often shortened in CeD participants. Crypts were grooves between villi that were often elongated in CeD participants. IELs were WBCs interspersed between epithelial cells of intestine where they function to preserve integrity of mucosal barrier by protecting epithelium against pathogen/immune-induced pathology. Decreased Vh:Cd ratio and increased IELs count indicated more extreme CeD symptoms. Baseline value: last observed value before first dose of gluten. Tr: T cell value taken before first dose of gluten. T6: T cell value at Day 6. T15: T cell value at Day 15.
Outcome measures
| Measure |
Group A: Gluten 3 Gram
n=7 Participants
Gluten 3 gram, powder, orally, once daily up to 14 days.
|
Group B: Gluten 10 Gram
n=7 Participants
Gluten 10 gram, powder, orally, once daily up to 14 days.
|
|---|---|---|
|
Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
Tr: Baseline Vh:Cd ratio
|
-0.0355 correlation coefficient
|
0.1480 correlation coefficient
|
|
Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
Tr: Baseline IEL counts
|
-0.0050 correlation coefficient
|
-0.0905 correlation coefficient
|
|
Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
T6: Day 15 Vh: Cd ratio
|
0.0368 correlation coefficient
|
-0.0170 correlation coefficient
|
|
Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
T6: Day 15 IEL counts
|
0.2179 correlation coefficient
|
0.0595 correlation coefficient
|
|
Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
T15: Day 15 Vh: Cd ratio
|
-0.0913 correlation coefficient
|
0.0214 correlation coefficient
|
|
Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
T15: Day 15 IEL counts
|
0.2967 correlation coefficient
|
0.0192 correlation coefficient
|
SECONDARY outcome
Timeframe: Baseline and Day 6Population: The biomarker analysis set consisted of all participants who had two endoscopic examinations with biopsies, one before and one after gluten challenge.
ELISpot assay and gluten specific TCR measures drug response by quantifying changes in the number or function of gluten-specific T cells. Baseline value was defined as the last observed value before the first dose of gluten.
Outcome measures
| Measure |
Group A: Gluten 3 Gram
n=7 Participants
Gluten 3 gram, powder, orally, once daily up to 14 days.
|
Group B: Gluten 10 Gram
n=7 Participants
Gluten 10 gram, powder, orally, once daily up to 14 days.
|
|---|---|---|
|
Change From Baseline in Gluten-specific T Cells in Blood Based on Enzyme-linked Immune Absorbent Spot (ELISPot) Assay and T Cell Receptor (TCR) Human Leukocyte Antigen Serotype (HLA-DQ2)-Tetramers
Baseline (ELISpot)
|
1.00 per million CD4+ T cells
Standard Deviation 1.956
|
1.45 per million CD4+ T cells
Standard Deviation 1.756
|
|
Change From Baseline in Gluten-specific T Cells in Blood Based on Enzyme-linked Immune Absorbent Spot (ELISPot) Assay and T Cell Receptor (TCR) Human Leukocyte Antigen Serotype (HLA-DQ2)-Tetramers
Change at Day 6 (ELISpot)
|
3.83 per million CD4+ T cells
Standard Deviation 6.902
|
25.12 per million CD4+ T cells
Standard Deviation 29.025
|
|
Change From Baseline in Gluten-specific T Cells in Blood Based on Enzyme-linked Immune Absorbent Spot (ELISPot) Assay and T Cell Receptor (TCR) Human Leukocyte Antigen Serotype (HLA-DQ2)-Tetramers
Baseline (Tetramer)
|
34.62 per million CD4+ T cells
Standard Deviation 29.215
|
17.33 per million CD4+ T cells
Standard Deviation 14.894
|
|
Change From Baseline in Gluten-specific T Cells in Blood Based on Enzyme-linked Immune Absorbent Spot (ELISPot) Assay and T Cell Receptor (TCR) Human Leukocyte Antigen Serotype (HLA-DQ2)-Tetramers
Change at Day 6 (Tetramer)
|
26.76 per million CD4+ T cells
Standard Deviation 54.084
|
522.47 per million CD4+ T cells
Standard Deviation 788.177
|
Adverse Events
Group A: Gluten 3 Gram
Group B: Gluten 10 Gram
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group A: Gluten 3 Gram
n=9 participants at risk
Gluten 3 gram, powder, orally, once daily up to 14 days.
|
Group B: Gluten 10 Gram
n=7 participants at risk
Gluten 10 gram, powder, orally, once daily up to 14 days.
|
|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
11.1%
1/9 • Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
14.3%
1/7 • Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.1%
1/9 • Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/7 • Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/9 • Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
14.3%
1/7 • Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Metabolism and nutrition disorders
Gluten sensitivity
|
11.1%
1/9 • Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/7 • Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
- Publication restrictions are in place
Restriction type: OTHER