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Trial of Specific Carbohydrate and Mediterranean Diets to Induce Remission of Crohn's Disease (DINE-CD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03058679
Recruitment Status : Completed
First Posted : February 23, 2017
Results First Posted : July 21, 2021
Last Update Posted : July 21, 2021
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
Crohn's and Colitis Foundation
University of North Carolina, Chapel Hill
Information provided by (Responsible Party):
University of Pennsylvania

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Crohn Disease
Intervention Other: Diet
Enrollment 197
Recruitment Details The study was conducted in 33 clinical sites across the United States. Enrollment in the trial occurred between September 29, 2017 and October 8, 2019.
Pre-assignment Details There were 3 main reasons that participants who consented to the study were not randomized. The majority did not meet eligibility criteria. A small number withdrew or were lost to follow-up
Arm/Group Title Specific Carbohydrate Diet Mediterranean Style Diet
Hide Arm/Group Description Diet: food for the diet will be provided to the participants for 6 weeks Diet: food for the diet will be provided to the participants for 6 weeks
Period Title: Baseline to Week 6
Started 99 [1] 92 [2]
Completed 81 77
Not Completed 18 15
Reason Not Completed
Lost to Follow-up             3             2
Change in Crohn's disease medication             4             2
Adverse Event             6             6
Withdrawal by Subject             4             3
Difficulty following the diet             0             2
Physician Decision             1             0
[1]
3 randomized to SCD withdrew before starting diet;2 randomized pts w/ baseline sCDAI<150 excluded.
[2]
Due to an error 1 participant was randomized with a baseline sCDAI<150. This pt was excluded.
Period Title: Week 6 to Week 12
Started 81 77
Completed 61 60
Not Completed 20 17
Reason Not Completed
Change in medication             5             7
Adverse Event             4             3
Withdrawal by Subject             9             4
Difficulty following the assigned diet             2             3
Arm/Group Title Mediterranean Style Diet Specific Carbohydrate Diet Total
Hide Arm/Group Description Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks Total of all reporting groups
Overall Number of Baseline Participants 92 99 191
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 92 participants 99 participants 191 participants
37.0
(29.5 to 53.0)
36.0
(27.0 to 46.0)
37
(28.0 to 50.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
Female
63
  68.5%
58
  58.6%
121
  63.4%
Male
29
  31.5%
41
  41.4%
70
  36.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
Hispanic or Latino
4
   4.3%
4
   4.0%
8
   4.2%
Not Hispanic or Latino
88
  95.7%
92
  92.9%
180
  94.2%
Unknown or Not Reported
0
   0.0%
3
   3.0%
3
   1.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
Asian
0
   0.0%
2
   2.0%
2
   1.0%
Black
2
   2.2%
5
   5.1%
7
   3.7%
Multiracial
1
   1.1%
1
   1.0%
2
   1.0%
Other
3
   3.3%
1
   1.0%
4
   2.1%
Unknown
0
   0.0%
2
   2.0%
2
   1.0%
White
86
  93.5%
88
  88.9%
174
  91.1%
Body Mass Index (BMI)  
Median (Inter-Quartile Range)
Unit of measure:  Kg/m2
Number Analyzed 92 participants 99 participants 191 participants
25.1
(21.3 to 29.9)
25.6
(22.5 to 29.0)
25.3
(21.8 to 29.5)
Smoking status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
Never
68
  73.9%
79
  79.8%
147
  77.0%
Past
21
  22.8%
20
  20.2%
41
  21.5%
Current
3
   3.3%
0
   0.0%
3
   1.6%
Years since CD diagnosis  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 92 participants 99 participants 191 participants
10
(5 to 21)
10
(3 to 16)
10
(4 to 17)
CD behavior  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
Non-stricturing, nonpenetrating
56
  60.9%
60
  60.6%
116
  60.7%
Stricturing
19
  20.7%
17
  17.2%
36
  18.8%
Penetrating
9
   9.8%
13
  13.1%
22
  11.5%
Stricturing and penetrating
8
   8.7%
9
   9.1%
17
   8.9%
Crohn's disease distribution  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
Ileum alone
22
  23.9%
30
  30.3%
52
  27.2%
Colon alone
17
  18.5%
13
  13.1%
30
  15.7%
Ileum and Colon
53
  57.6%
55
  55.6%
108
  56.5%
Missing
0
   0.0%
1
   1.0%
1
   0.5%
History of perianal fistula  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
24
  26.1%
20
  20.2%
44
  23.0%
History of intestinal surgery  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
34
  37.0%
29
  29.3%
63
  33.0%
Current use of any biologic  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
55
  59.8%
53
  53.5%
108
  56.5%
Current use of immunomodulators  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
11
  12.0%
11
  11.1%
22
  11.5%
Current use of oral 5-ASA  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
6
   6.5%
15
  15.2%
21
  11.0%
Current use of rectal 5 ASA  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
0
   0.0%
3
   3.0%
3
   1.6%
Current use of oral steroids  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
3
   3.3%
11
  11.1%
14
   7.3%
Current use of rectal steroids  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
1
   1.1%
2
   2.0%
3
   1.6%
Number of prior anti-TNF medications  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
0
28
  30.4%
34
  34.3%
62
  32.5%
1
22
  23.9%
29
  29.3%
51
  26.7%
2
32
  34.8%
26
  26.3%
58
  30.4%
3
9
   9.8%
9
   9.1%
18
   9.4%
4
1
   1.1%
1
   1.0%
2
   1.0%
Prior ustekinumab  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
22
  23.9%
23
  23.2%
45
  23.6%
Prior vedolizumab  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
27
  29.3%
22
  22.2%
49
  25.7%
hsCRP mg/L  
Median (Inter-Quartile Range)
Unit of measure:  mg/L
Number Analyzed 92 participants 99 participants 191 participants
2.5
(1.2 to 6.2)
3.2
(1.4 to 8.1)
2.9
(1.4 to 7.5)
hsCRP >5 mg/L  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
28
  30.4%
37
  37.4%
65
  34.0%
fecal calprotectin (FC) ug/g  
Median (Inter-Quartile Range)
Unit of measure:  Ug/g
Number Analyzed 92 participants 99 participants 191 participants
40.0
(16.0 to 185.0)
107.5
(16.0 to 223.0)
70
(16.0 to 194.0)
fecal calprotectin (FC) >250 ug/g  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
13
  14.1%
23
  23.2%
36
  18.8%
Inflammation on colonoscopy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
Not performed
80
  87.0%
89
  89.9%
169
  88.5%
Yes
8
   8.7%
8
   8.1%
16
   8.4%
Probably
1
   1.1%
0
   0.0%
1
   0.5%
Probably not
1
   1.1%
1
   1.0%
2
   1.0%
No
2
   2.2%
1
   1.0%
3
   1.6%
FC>250 ug/g or hsCRP>5 mg/L or definite inflammation on colonoscopy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
38
  41.3%
50
  50.5%
88
  46.1%
sCDAI (median, Q1-Q3)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 92 participants 99 participants 191 participants
217.7
(195.7 to 247.0)
226.0
(197.0 to 263.8)
223.0
(195.7 to 259.6)
[1]
Measure Description: Short Crohn's Disease Activity Index. This is a method to measure Crohn's disease patient's symptoms using only a questionnaire,which can be completed without an office visit or lab work. The variables included in the short CDAI are abdominal pain, diarrhea frequency, and general well-being. The higher the score, the worse the disease activity. The sCDAI uses the same scale as the full CDAI, such that scores,<150 define remission, 150 to 219 mild activity, 220 to450 moderate activity, and.450 severe activity. The total score is reported.
CDAI (median, Q1-Q3)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 92 participants 99 participants 191 participants
206.8
(179.3 to 247.0)
210.0
(169.8 to 246.2)
209.5
(171.5 to 246.2)
[1]
Measure Description:

The Crohn's Disease Activity Index - CDAI scores range from 0 to 600. A score of less than 150 denotes relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease. The higher the score, the worse the disease activity.

This index uses the following variables to determine a score: number of stools, abdominal pain, general well-being, extraintestinal complications, antidiarrheal agents used in the previous 7 days, abdominal mass felt on palpation, hematocrit, and body weight

Short IBDQ (median, Q1-Q3)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 92 participants 99 participants 191 participants
38.0
(33.0 to 44.0)
40.0
(33.0 to 45.0)
39.0
(33.0 to 45.0)
[1]
Measure Description: The SIBDQ is a 10-item health-related quality of life (HRQOL) questionnaire validated for use in CD patients. It assesses physical, social, and emotional status and is scored on a 7-point Likert scale from 1 (severe problem) to 7 (no problems at all). Scores for each question are summed to provide a total score. The total score is reported. The absolute score ranges from 10 (poor HRQOL) to 70 (optimum HRQOL).
PROMIS measures (median, Q1-Q3)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 92 participants 99 participants 191 participants
Fatigue
60.4
(55.9 to 65.9)
58.9
(54.8 to 65.6)
59.6
(55.0 to 65.8)
Pain interference
60.1
(55.7 to 63.8)
61.3
(55.7 to 63.6)
61.2
(55.7 to 63.7)
Sleep disturbance
57.3
(51.4 to 62.1)
54.5
(49.4 to 60.2)
56.0
(50.9 to 61.4)
Social isolation
48.4
(41.0 to 56.1)
47.2
(34.8 to 53.8)
47.9
(34.8 to 54.5)
[1]
Measure Description: Patient-Reported Outcomes Measurement Information System (PROMIS)- set of person-centered measures that evaluate and monitor health status. All assessments are for the last 7 days. To calculate a total raw score, each item is scored on a scale of 1-5. If the form has 7 items, the lowest possible raw score is 7 and the highest possible raw score is 35. Raw scores are then translated into T scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. T-scores are reported. Higher T-scores denote worse outcomes.
Inflammatory back pain screen   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 99 participants 191 participants
0
30
  32.6%
40
  40.4%
70
  36.6%
1-3
39
  42.4%
40
  40.4%
79
  41.4%
>3
22
  23.9%
18
  18.2%
40
  20.9%
Missing
1
   1.1%
1
   1.0%
2
   1.0%
[1]
Measure Description: This self-reported survey assessed five criteria defining possible inflammatory back pain:(1) improvement with exercise (2) pain at night (3) insidious onset (4) age at onset <40 years and (5) no improvement with rest. The higher the score the more likely the person had inflammatory back pain.
AMeD Score   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 92 participants 99 participants 191 participants
3.0
(1.0 to 4.0)
2.0
(1.0 to 3.0)
3.0
(2.0 to 4.0)
[1]
Measure Description: Alternate Mediterranean Diet Score - Participants completed a 24-hour dietary recall at baseline, during week 6 and during week 12. These data were used to compute the Alternate Mediterranean Diet Score (AMeD) where a higher score implies greater consistency with a Mediterranean diet. AMeD scores range from 0 (minimal adherence) to 9 (maximal adherence).
1.Primary Outcome
Title Percentage of Participants That Achieved Symptomatic Remission at Week 6
Hide Description Assessed by Short Crohn's Disease Activity Index (sCDAI) - diarrhea, abdominal pain and general well being; sCDAI <150 in the absence of initiation or increase of any CD medications
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
percentage of participants who achieved symptomatic remission at week 6
Arm/Group Title Mediterranean Style Diet Specific Carbohydrate Diet
Hide Arm/Group Description:
Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
Overall Number of Participants Analyzed 92 99
Measure Type: Count of Participants
Unit of Measure: Participants
40
  43.5%
46
  46.5%
2.Primary Outcome
Title Reduction in Bowel Inflammation Among Those Whose Screening Fecal Calprotectin (FC) Was Greater Than 250μg/g at Baseline and Who Had an FC Results at Both Baseline and Week 6
Hide Description reduction of calprotectin to less than 250 μg/g and by greater than 50% from screening among those with screening FC >250 μg/g
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This measure includes only those whose screening fecal calprotectin (FC) was greater than 250μg/g at baseline and who had an FC results at both baseline and week 6
Arm/Group Title Mediterranean Style Diet Specific Carbohydrate Diet
Hide Arm/Group Description:
Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
Overall Number of Participants Analyzed 13 23
Measure Type: Count of Participants
Unit of Measure: Participants
4
  30.8%
8
  34.8%
3.Secondary Outcome
Title Percentage of Participants That Reached Clinical Remission at Week 6
Hide Description Assessed by the CDAI - CDAI <150
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mediterranean Style Diet Specific Carbohydrate Diet
Hide Arm/Group Description:
Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
Overall Number of Participants Analyzed 92 99
Measure Type: Count of Participants
Unit of Measure: Participants
44
  47.8%
48
  48.5%
4.Secondary Outcome
Title Percentage of Participants With a Reduction in Systemic Inflammation at Week 6
Hide Description reduction in high-sensitivity CRP (hsCRP) to <5 mg/L and >50% reduction from screening among those with screening hsCRP >5mg/L
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This measure includes only those that had a screening hsCRP > 5mg/L and had hsCRP measured at both screening and at week 6
Arm/Group Title Mediterranean Style Diet Specific Carbohydrate Diet
Hide Arm/Group Description:
Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
Overall Number of Participants Analyzed 28 37
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.6%
2
   5.4%
Time Frame AEs were recorded at each study contact from screening visit to a participant's end of study visit. For participants that completed the study, AEs were assessed at screening, baseline, wk 6 and week 12. Among participants who withdrew early from the study, AEs were assessed at the above named timepoints until the time of withdraw. The clinical course of each AE was followed until resolution, stabilization, or until it was determined that study intervention or participation was not the cause.
Adverse Event Reporting Description As per the DINE-CD protocol, allergic reaction to a component of the food, intolerance of the food other than allergic reaction, worsening of CD and worsening of extraintestinal manifestations of CD was considered expected. AEs were included for all randomized participants who started the diet with the exception of 3 participant who were randomized in error with an sCDAI <150 (as noted in the participant flow).
 
Arm/Group Title Mediterranean Style Diet Specific Carbohydrate Diet
Hide Arm/Group Description Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks Diet: food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks
All-Cause Mortality
Mediterranean Style Diet Specific Carbohydrate Diet
Affected / at Risk (%) Affected / at Risk (%)
Total   0/92 (0.00%)      0/99 (0.00%)    
Hide Serious Adverse Events
Mediterranean Style Diet Specific Carbohydrate Diet
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/92 (5.43%)      3/99 (3.03%)    
Gastrointestinal disorders     
Small intestinal obstruction  1  1/92 (1.09%)  1 1/99 (1.01%)  1
Abdominal pain  1  3/92 (3.26%)  3 1/99 (1.01%)  3
Worsening of Crohn's disease  1  0/92 (0.00%)  0 2/99 (2.02%)  2
Rectal hemorrhage  1  1/92 (1.09%)  1 0/99 (0.00%)  0
Diarrhea  1  1/92 (1.09%)  1 0/99 (0.00%)  0
Nausea  1  1/92 (1.09%)  1 0/99 (0.00%)  0
Vomiting  1  1/92 (1.09%)  1 0/99 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Mediterranean Style Diet Specific Carbohydrate Diet
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/92 (19.57%)      19/99 (19.19%)    
Gastrointestinal disorders     
Abdominal pain  1  13/92 (14.13%)  14 10/99 (10.10%)  11
Diarrhea  1  7/92 (7.61%)  7 5/99 (5.05%)  5
Gastrointestingal disorders other - Worsening of Crohn's disease symptons  1  4/92 (4.35%)  4 6/99 (6.06%)  7
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. James D. Lewis
Organization: University of Pennsylvania
Phone: 215-573-5137
EMail: lewisjd@pennmedicine.upenn.edu
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03058679    
Other Study ID Numbers: 825907
First Submitted: February 16, 2017
First Posted: February 23, 2017
Results First Submitted: March 26, 2021
Results First Posted: July 21, 2021
Last Update Posted: July 21, 2021