Trial Outcomes & Findings for Serum Markers in Gluten Challenge (NCT NCT00931892)
NCT ID: NCT00931892
Last Updated: 2021-06-04
Results Overview
Histological evaluation of duodenal biopsy samples to evaluate crypt depth to villous height ratio. On the best oriented section of each biopsy fragment, villous height to crypt depth (Vh:Cd) ratio was determined by measuring the mean height /mean depth of adjacent villi/proliferative crypt zones at magnification 100x. Evaluations were considered discrepant Vh:Cd differed by more than 0.5. Overall, there was excellent concordance with the evaluations of the 165 biopsy fragments determined to be optimal for evaluation. The Vh:Cd ratios on individual biopsies from a single averaged to produce a representative Vh:Cd ratio for each endoscopy. Normal Vh:Cd ratio was regarded as 3:1 or greater. Adelman DC, Murray J, Wu TT, Mäki M, Green PH, Kelly CP. Measuring Change In Small Intestinal Histology In Patients With Celiac Disease. Am J Gastroenterol. 2018 Mar;113(3):339-347. doi: 10.1038/ajg.2017.480. Epub 2018 Feb 20. Review. PubMed PMID: 29460921.
COMPLETED
NA
21 participants
Screening (Day -7 to -14), Day 3, Day 14
2021-06-04
Participant Flow
21 patients were enrolled in the study. 1 patient was found to be negative for DQ2 and DQ8, therefore did not have Celiac disease. This patient was excluded from the study. Therefore, for the study we had a total of 20 participants.
Participant milestones
| Measure |
Low Gluten Group
Subjects will eat 3g of gluten per day
Gluten: 3g
|
High Gluten Group
Subjects will eat 10g of gluten per day
Gluten: 10g
|
|---|---|---|
|
Completed Gluten Challenge
STARTED
|
10
|
10
|
|
Completed Gluten Challenge
COMPLETED
|
10
|
10
|
|
Completed Gluten Challenge
NOT COMPLETED
|
0
|
0
|
|
Completed Endoscopies
STARTED
|
10
|
10
|
|
Completed Endoscopies
First Endoscopy
|
10
|
10
|
|
Completed Endoscopies
Second Endoscopy
|
10
|
10
|
|
Completed Endoscopies
Third Endoscopy
|
10
|
9
|
|
Completed Endoscopies
COMPLETED
|
10
|
9
|
|
Completed Endoscopies
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Low Gluten Group
Subjects will eat 3g of gluten per day
Gluten: 3g
|
High Gluten Group
Subjects will eat 10g of gluten per day
Gluten: 10g
|
|---|---|---|
|
Completed Endoscopies
Patient did not complete third endoscopy due to discomfort
|
0
|
1
|
Baseline Characteristics
Serum Markers in Gluten Challenge
Baseline characteristics by cohort
| Measure |
Low Gluten Group
n=10 Participants
Participants meeting inclusion criteria were randomized into the low gluten group. These participants ate two slices of wheat bread per day (3 g of gluten). Bread was procured from a standard source and gluten dose tested using the RIDASCREEN Gliadin R5 antibody ELISA. The study included a 14-day run-in period followed by a 14 day gluten challenge and a final visit 14 days post-gluten challenge. Other than the dispensed bread, subjects were instructed to remain on their gluten-free diet throughout the duration of the study.
Gluten: 3g
|
High Gluten Group
n=10 Participants
Participants meeting inclusion criteria were randomized into the low gluten group. These participants ate five slices of wheat bread per day (10 g of gluten). Bread was procured from a standard source and gluten dose tested using the RIDASCREEN Gliadin R5 antibody ELISA. The study included a 14-day run-in period followed by a 14 day gluten challenge and a final visit 14 days post-gluten challenge. Other than the dispensed bread, subjects were instructed to remain on their gluten-free diet throughout the duration of the study.
Gluten: 10g
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
48.8 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
38.8 years
STANDARD_DEVIATION 13.1 • n=7 Participants
|
43.3 years
STANDARD_DEVIATION 13.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 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
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 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
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 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
|
10 Participants
n=7 Participants
|
19 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
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Age at Celiac Diagnosis
|
45.4 years
STANDARD_DEVIATION 13.9 • n=5 Participants
|
31.0 years
STANDARD_DEVIATION 11.7 • n=7 Participants
|
35.7 years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
|
Months since Celiac Disease diagnosis
|
42.3 months
STANDARD_DEVIATION 21.3 • n=5 Participants
|
92.5 months
STANDARD_DEVIATION 49.1 • n=7 Participants
|
62.3 months
STANDARD_DEVIATION 87.1 • n=5 Participants
|
|
Laboratory Characteristics
HLA DQ2
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Laboratory Characteristics
HLA DQ8
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Laboratory Characteristics
HLA DQ2 + DQ 8
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Laboratory Characteristics
HLA A1 * 05 alone
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Villous height to crypt depth ratio
|
2.05 unitless
STANDARD_DEVIATION 0.80 • n=5 Participants
|
4.33 unitless
STANDARD_DEVIATION 6.69 • n=7 Participants
|
2.21 unitless
STANDARD_DEVIATION 0.8 • n=5 Participants
|
|
Mean number of Intraepithelial lymphocytes
|
37.10 unitless
STANDARD_DEVIATION 13.66 • n=5 Participants
|
28.4 unitless
STANDARD_DEVIATION 13.3 • n=7 Participants
|
32.59 unitless
STANDARD_DEVIATION 15.1 • n=5 Participants
|
|
Baseline tissue transglutaminase (tTG)
|
13.76 units
STANDARD_DEVIATION 8.30 • n=5 Participants
|
8.27 units
STANDARD_DEVIATION 5.70 • n=7 Participants
|
11.00 units
STANDARD_DEVIATION 7.50 • n=5 Participants
|
|
Baseline Deamidated gliadin peptide (DGP)
|
6.70 units
STANDARD_DEVIATION 2.59 • n=5 Participants
|
14.04 units
STANDARD_DEVIATION 26.49 • n=7 Participants
|
10.90 units
STANDARD_DEVIATION 19.60 • n=5 Participants
|
|
Baseline Celiac Dietary Adherence test (CDAT)
|
11.33 scores on a scale
STANDARD_DEVIATION 3.2 • n=5 Participants
|
11.40 scores on a scale
STANDARD_DEVIATION 2.9 • n=7 Participants
|
11.37 scores on a scale
STANDARD_DEVIATION 2.9 • n=5 Participants
|
|
Baseline Celiac Symptom Index (CSI)
|
28.50 scores on a scale
STANDARD_DEVIATION 5.78 • n=5 Participants
|
22.50 scores on a scale
STANDARD_DEVIATION 4.99 • n=7 Participants
|
25.26 scores on a scale
STANDARD_DEVIATION 5.90 • n=5 Participants
|
|
Baseline Gastrointestinal Symptom Rating Scale (GSRS)
|
22.88 scores on a scale
STANDARD_DEVIATION 9.58 • n=5 Participants
|
19.20 scores on a scale
STANDARD_DEVIATION 3.26 • n=7 Participants
|
20.32 scores on a scale
STANDARD_DEVIATION 5.10 • n=5 Participants
|
|
Baseline Quality of Life Visual Analog Scale (VAS)
|
80.00 scores on a scale
STANDARD_DEVIATION 13.10 • n=5 Participants
|
84.40 scores on a scale
STANDARD_DEVIATION 12.10 • n=7 Participants
|
82.20 scores on a scale
STANDARD_DEVIATION 12.50 • n=5 Participants
|
PRIMARY outcome
Timeframe: Screening (Day -7 to -14), Day 3, Day 14Population: Subjects with biopsy proven celiac disease in remission were enrolled. For Day 3, 17 subjects had evaluable pathology biopsies. On Day 14, 19 participants had evaluable pathology biopsies.
Histological evaluation of duodenal biopsy samples to evaluate crypt depth to villous height ratio. On the best oriented section of each biopsy fragment, villous height to crypt depth (Vh:Cd) ratio was determined by measuring the mean height /mean depth of adjacent villi/proliferative crypt zones at magnification 100x. Evaluations were considered discrepant Vh:Cd differed by more than 0.5. Overall, there was excellent concordance with the evaluations of the 165 biopsy fragments determined to be optimal for evaluation. The Vh:Cd ratios on individual biopsies from a single averaged to produce a representative Vh:Cd ratio for each endoscopy. Normal Vh:Cd ratio was regarded as 3:1 or greater. Adelman DC, Murray J, Wu TT, Mäki M, Green PH, Kelly CP. Measuring Change In Small Intestinal Histology In Patients With Celiac Disease. Am J Gastroenterol. 2018 Mar;113(3):339-347. doi: 10.1038/ajg.2017.480. Epub 2018 Feb 20. Review. PubMed PMID: 29460921.
Outcome measures
| Measure |
Baseline (Day -14) Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Baseline (Day -14) High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 3 Low Gluten Group
n=8 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day.
|
Day 3 High Gluten Group
n=9 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Day 14 High Gluten Group
n=9 Participants
Villous height to crypt depth ratio in high gluten group.
In the high gluten group subjects consume 10 grams of gluten per day.
|
Day 7 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 7 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 14 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 28 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 28 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Crypt Depth to Villous Height Ratio
|
2.05 ratio
Standard Deviation 0.80
|
4.33 ratio
Standard Deviation 6.69
|
1.19 ratio
Standard Deviation 0.67
|
2.02 ratio
Standard Deviation 0.99
|
0.98 ratio
Standard Deviation 0.85
|
1.26 ratio
Standard Deviation 1.08
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Screening (Day -7 to -14), Day 3, Day 14Population: Subjects with biopsy proven celiac disease in remission were enrolled. For Day 3, 17 subjects had evaluable pathology biopsies. On Day 14, 19 participants had evaluable pathology biopsies.
On the best oriented section of each biopsy fragment , the number of intraepithelial lymphocytes (IEL count) per 100 enterocytes was recorded at magnification 400x. IEL counts were considered discrepant if a difference of \>10 IELs existed between counts. Overall, there was excellent concordance with the evaluations of the 165 biopsy fragments determined to be optimal for evaluation. The IEL counts on individual biopsies from a single endoscopy were averaged to produce a representative IEL count for each endoscopy. Adelman DC, Murray J, Wu TT, Mäki M, Green PH, Kelly CP. Measuring Change In Small Intestinal Histology In Patients With Celiac Disease. Am J Gastroenterol. 2018 Mar;113(3):339-347. doi: 10.1038/ajg.2017.480. Epub 2018 Feb 20. Review. PubMed PMID: 29460921.
Outcome measures
| Measure |
Baseline (Day -14) Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Baseline (Day -14) High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 3 Low Gluten Group
n=8 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day.
|
Day 3 High Gluten Group
n=9 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Day 14 High Gluten Group
n=9 Participants
Villous height to crypt depth ratio in high gluten group.
In the high gluten group subjects consume 10 grams of gluten per day.
|
Day 7 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 7 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 14 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 28 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 28 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Count of Intraepithelial Lymphocytes Per 100 Enterocytes in Duodenal Biopsy Samples
|
37.08 Count of Lymphocytes Per 100 Enterocytes
Standard Deviation 13.66
|
28.91 Count of Lymphocytes Per 100 Enterocytes
Standard Deviation 15.81
|
44.89 Count of Lymphocytes Per 100 Enterocytes
Standard Deviation 20.49
|
30.68 Count of Lymphocytes Per 100 Enterocytes
Standard Deviation 18.09
|
47.95 Count of Lymphocytes Per 100 Enterocytes
Standard Deviation 14.30
|
52.36 Count of Lymphocytes Per 100 Enterocytes
Standard Deviation 28.52
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28Population: Subjects with biopsy proven celiac disease in remission were enrolled. Measures of intestinal permeability (urinary lactulose to mannitol ratio) (LAMA) . Four participants were unable to tolerate LAMA testing due to gastrointestinal symptoms.
LAMA evaluation has been reported to be an accurate measure of small intestinal mucosal permeability though assessment of differential absorption of lactulose and mannitol. For LAMA testing, a solution containing 7.5 g lactulose and 2 g mannitol in 100 mL of water was ingested by the participants in the evening after visit 1 and in the evening before each other study visit. The participants were asked to fast for at least 4 h and to void completely before drinking the sugar solution, then fast overnight and collect all overnight and morning urine. Urine sample analyzed for lactulose and mannitol using standardized methodology by liquid chromatography-tandem mass spectrometry.
Outcome measures
| Measure |
Baseline (Day -14) Low Gluten Group
n=8 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Baseline (Day -14) High Gluten Group
n=8 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 3 Low Gluten Group
n=8 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day.
|
Day 3 High Gluten Group
n=8 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Group
n=8 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Day 14 High Gluten Group
n=7 Participants
Villous height to crypt depth ratio in high gluten group.
In the high gluten group subjects consume 10 grams of gluten per day.
|
Day 7 Low Gluten Dose Group
n=8 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 7 High Gluten Dose Group
n=7 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Dose Group
n=8 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 14 High Gluten Dose Group
n=6 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 28 Low Gluten Dose Group
n=8 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 28 High Gluten Dose Group
n=7 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Measures of Intestinal Permeability (Urinary Lactulose to Mannitol Ratio)
|
0.23 ratio
Standard Deviation 0.17
|
0.24 ratio
Standard Deviation 0.25
|
0.65 ratio
Standard Deviation 1.15
|
0.17 ratio
Standard Deviation 0.15
|
0.25 ratio
Standard Deviation 0.15
|
0.44 ratio
Standard Deviation 0.60
|
0.45 ratio
Standard Deviation 0.71
|
0.29 ratio
Standard Deviation 0.28
|
0.89 ratio
Standard Deviation 1.53
|
0.59 ratio
Standard Deviation 0.52
|
0.29 ratio
Standard Deviation 0.24
|
0.57 ratio
Standard Deviation 0.82
|
SECONDARY outcome
Timeframe: Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28Population: Subjects with biopsy proven celiac disease in remission were enrolled.
IgA anti-human tissue transglutaminase assay (Inova Diagnostics, Inc., San Diego, USA): negative \<20, borderline 20-30, positive \>30. IgA/IgG anti- DGP assay : NEGATIVE \<20, BORDERLINE 20-30, POSITIVE \>30 METHOD IS INOVA ANTI-DEAMIDATED GLIADIN PEPTIDE IGA/IGG.
Outcome measures
| Measure |
Baseline (Day -14) Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Baseline (Day -14) High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 3 Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day.
|
Day 3 High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Day 14 High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group.
In the high gluten group subjects consume 10 grams of gluten per day.
|
Day 7 Low Gluten Dose Group
n=10 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 7 High Gluten Dose Group
n=10 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Dose Group
n=10 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 14 High Gluten Dose Group
n=10 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 28 Low Gluten Dose Group
n=10 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 28 High Gluten Dose Group
n=10 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Measures of Immune Activation
IgA anti-tTG
|
6.70 units on a scale
Standard Deviation 2.60
|
10.34 units on a scale
Standard Deviation 5.75
|
13.76 units on a scale
Standard Deviation 10.88
|
11.50 units on a scale
Standard Deviation 6.63
|
11.84 units on a scale
Standard Deviation 9.50
|
10.34 units on a scale
Standard Deviation 5.75
|
13.77 units on a scale
Standard Deviation 10.90
|
11.50 units on a scale
Standard Deviation 6.63
|
12.63 units on a scale
Standard Deviation 8.73
|
15.16 units on a scale
Standard Deviation 10.30
|
37.81 units on a scale
Standard Deviation 45.07
|
43.20 units on a scale
Standard Deviation 53.77
|
|
Measures of Immune Activation
IgA/IgG anti- DGP
|
6.70 units on a scale
Standard Deviation 2.60
|
14.04 units on a scale
Standard Deviation 26.49
|
7.83 units on a scale
Standard Deviation 2.54
|
14.69 units on a scale
Standard Deviation 27.01
|
12.95 units on a scale
Standard Deviation 8.26
|
14.04 units on a scale
Standard Deviation 26.49
|
7.83 units on a scale
Standard Deviation 2.54
|
14.69 units on a scale
Standard Deviation 27.01
|
17.81 units on a scale
Standard Deviation 22.97
|
22.74 units on a scale
Standard Deviation 29.31
|
45.42 units on a scale
Standard Deviation 62.56
|
41.95 units on a scale
Standard Deviation 33.91
|
SECONDARY outcome
Timeframe: Screening (Day -7 to -14), Day 3, Day 14Population: All 20 subjects were included for the tTG and DGP analysis. For Day 28 High Gluten Challenge Dose Group, 1 participant had both a tTG and DGP \>20 which is why the count is greater than the number analyzed.
Proportion of participants responding to a gluten challenge. Tissue transglutaminase (tTG) scoring: NEGATIVE \<20, BORDERLINE 20-30, POSITIVE \>30. Deamidated gliadin peptide (DGP) scoring: NEGATIVE \<20, BORDERLINE 20-30, POSITIVE \>30 METHOD IS INOVA ANTI-DEAMIDATED GLIADIN PEPTIDE IGA/IGG.
Outcome measures
| Measure |
Baseline (Day -14) Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Baseline (Day -14) High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 3 Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day.
|
Day 3 High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Group
n=20 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Day 14 High Gluten Group
n=20 Participants
Villous height to crypt depth ratio in high gluten group.
In the high gluten group subjects consume 10 grams of gluten per day.
|
Day 7 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 7 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 14 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 28 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 28 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Assessment of Protein Expression in Intestinal Biopsies
tTG > 20
|
3 Participants
|
2 Participants
|
5 Participants
|
6 Participants
|
8 Participants
|
8 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Assessment of Protein Expression in Intestinal Biopsies
DGP > 20
|
2 Participants
|
4 Participants
|
4 Participants
|
5 Participants
|
6 Participants
|
9 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Assessment of Protein Expression in Intestinal Biopsies
tTG > 20 or DGP > 20
|
5 Participants
|
6 Participants
|
9 Participants
|
10 Participants
|
14 Participants
|
17 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28Population: Subjects with biopsy proven celiac disease in remission were enrolled. On Day -14, one subject in the high gluten dose group missed the CSI. On Day 7 one subject in the high gluten dose group missed the CSI. On Day 14 one subject in the high gluten dose group missed the CSI. On Day 28, one subject in the high gluten dose group and one subject in the low gluten dose missed the CSI.
CSI (Celiac Symptom Index) scores range from 7-80. Higher scores indicate greater degree of symptoms CSI: Leffler DA, Dennis M, Edwards George J, Jamma S, Cook EF, Schuppan D, Kelly CP. A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol. 2009;7:1328-34. PubMed PMID: 19665584.
Outcome measures
| Measure |
Baseline (Day -14) Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Baseline (Day -14) High Gluten Group
n=9 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 3 Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day.
|
Day 3 High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Day 14 High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group.
In the high gluten group subjects consume 10 grams of gluten per day.
|
Day 7 Low Gluten Dose Group
n=10 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 7 High Gluten Dose Group
n=9 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Dose Group
n=10 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 14 High Gluten Dose Group
n=9 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 28 Low Gluten Dose Group
n=9 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 28 High Gluten Dose Group
n=9 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Symptomatic Response to Gluten Exposure Determined by Celiac Symptom Index Questionnaire
|
28.5 score on a scale
Standard Deviation 5.78
|
22.5 score on a scale
Standard Deviation 4.99
|
28.44 score on a scale
Standard Deviation 6.44
|
23.00 score on a scale
Standard Deviation 5.29
|
30.33 score on a scale
Standard Deviation 7.81
|
27.54 score on a scale
Standard Deviation 10.27
|
31.11 score on a scale
Standard Deviation 7.90
|
28.80 score on a scale
Standard Deviation 13.36
|
31.38 score on a scale
Standard Deviation 11.40
|
31.00 score on a scale
Standard Deviation 12.70
|
26.88 score on a scale
Standard Deviation 7.70
|
23.90 score on a scale
Standard Deviation 6.740
|
SECONDARY outcome
Timeframe: Screening (Day -7 to -14), Day 3, Day 14Population: Only 19 subjects were evaluated for Marsh scores because one patient had a single endoscopy which did not produce evaluable samples.
Proportion of participants responding to a gluten challenge. Tissue transglutaminase (tTG) scoring: NEGATIVE \<20, BORDERLINE 20-30, POSITIVE \>30. Deamidated gliadin peptide (DGP) scoring: NEGATIVE \<20, BORDERLINE 20-30, POSITIVE \>30 METHOD IS INOVA ANTI-DEAMIDATED GLIADIN PEPTIDE IGA/IGG.
Outcome measures
| Measure |
Baseline (Day -14) Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Baseline (Day -14) High Gluten Group
n=9 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 3 Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day.
|
Day 3 High Gluten Group
n=9 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Group
n=20 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Day 14 High Gluten Group
n=19 Participants
Villous height to crypt depth ratio in high gluten group.
In the high gluten group subjects consume 10 grams of gluten per day.
|
Day 7 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 7 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 14 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 28 Low Gluten Dose Group
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 28 High Gluten Dose Group
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Assessment of Protein Expression in Intestinal Biopsies Using Marsh Scores
Marsh III
|
5 Participants
|
8 Participants
|
0 Participants
|
0 Participants
|
5 Participants
|
8 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Assessment of Protein Expression in Intestinal Biopsies Using Marsh Scores
Marsh III or tTG >20
|
8 Participants
|
9 Participants
|
5 Participants
|
6 Participants
|
13 Participants
|
16 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Assessment of Protein Expression in Intestinal Biopsies Using Marsh Scores
Marsh III or DGP > 20
|
7 Participants
|
9 Participants
|
4 Participants
|
5 Participants
|
11 Participants
|
17 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Assessment of Protein Expression in Intestinal Biopsies Using Marsh Scores
Marsh III or DGP > 20 or tTG > 20
|
10 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
19 Participants
|
19 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28Population: Subjects with biopsy proven celiac disease in remission were enrolled. On Day -14, one subject in the high gluten group missed completing the GSRS. On Day 0, two subjects (one in the low gluten group and one subject in the high gluten group) missed completing the GSRS. On Day 7, one subject in the high gluten group missed completing the GSRS. On Day 14, one subject in the high gluten group missed completing the GSRS. On Day 28, one subject in the high gluten group missed completing the GSRS.
Measure Description: GSRS (Gastrointestinal Symptom Rating Scale) scores range 15-105 with higher scores indicating greater degree of symptoms GSRS: Svedlund J, Sjödin I, Dotevall G. GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988;33(2):129-134. doi:10.1007/BF01535722
Outcome measures
| Measure |
Baseline (Day -14) Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Baseline (Day -14) High Gluten Group
n=9 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 3 Low Gluten Group
n=9 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day.
|
Day 3 High Gluten Group
n=9 Participants
Villous height to crypt depth ratio in high gluten group
In the high gluten group, subjects consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Group
n=10 Participants
Villous height to crypt depth ratio in low gluten group
In the low gluten group, subjects consumed 3 grams of gluten per day
|
Day 14 High Gluten Group
n=10 Participants
Villous height to crypt depth ratio in high gluten group.
In the high gluten group subjects consume 10 grams of gluten per day.
|
Day 7 Low Gluten Dose Group
n=10 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 7 High Gluten Dose Group
n=9 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 14 Low Gluten Dose Group
n=10 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 14 High Gluten Dose Group
n=9 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
Day 28 Low Gluten Dose Group
n=10 Participants
Subjects in the low gluten dose group consumed 3 grams of gluten per day.
|
Day 28 High Gluten Dose Group
n=9 Participants
Subjects in the high gluten dose group consumed 10 grams of gluten per day.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Symptomatic Response to Gluten Exposure Determined by Gastrointestinal Symptom Rating Scale
|
21.63 score on a scale
Standard Deviation 7.05
|
19.20 score on a scale
Standard Deviation 3.26
|
22.88 score on a scale
Standard Deviation 9.58
|
18.40 score on a scale
Standard Deviation 3.06
|
30.22 score on a scale
Standard Deviation 11.63
|
26.45 score on a scale
Standard Deviation 13.18
|
28.22 score on a scale
Standard Deviation 9.87
|
27.30 score on a scale
Standard Deviation 14.94
|
31.00 score on a scale
Standard Deviation 13.71
|
31.00 score on a scale
Standard Deviation 17.09
|
23.89 score on a scale
Standard Deviation 11.59
|
19.40 score on a scale
Standard Deviation 4.33
|
Adverse Events
Low Gluten Group
High Gluten Group
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Low Gluten Group
n=10 participants at risk
Subjects will eat 3g of gluten per day
Gluten: 3g
|
High Gluten Group
n=10 participants at risk
Subjects will eat 10g of gluten per day
Gluten: 10g
|
|---|---|---|
|
Gastrointestinal disorders
Nausea and vomiting
|
10.0%
1/10 • Number of events 1 • 4 weeks after participant received first dose
|
0.00%
0/10 • 4 weeks after participant received first dose
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place