A Pilot Study Examining Diet in Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis Clinical Trial

— DINER  

Official title:

A Pilot Study Examining a Vegan/Low-Sulfur Diet Versus the Specific Carbohydrate Diet in Patients With Primary Sclerosing Cholangitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04678219
• Other study ID #: 2019P002075
• Status: Recruiting
• Phase: N/A
• Start date: August 28, 2020
• Est. completion date: December 2021

Study information

• Verified date: December 2020
• Source: Brigham and Women's Hospital
• Contact: Nadine Javier
• Phone: 617-732-9481
• Email: njavier[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study is exploring the effects of dietary intervention in PSC. Study participants will be randomly assigned to either the Specific Carbohydrate Diet (SCD) or a vegan/low-sulfur diet for 8 weeks; the entire study will last approximately 14 weeks. Participants will work with BWH Registered Dieticians and receive dietary educational materials, recipes, and a food procurement stipend to support the new diet. Subjects will attend 7 video visits and have regular lab tests performed, requiring blood and stool samples.

Description:

The chronic, autoimmune liver disease Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic, hepatobiliary disease characterized by inflammation and fibrosis of the bile duct. As the disease progresses, it may result in debilitating bile duct cirrhosis, malignancy, and liver failure. Although the list of drugs studied for the treatment of PSC is extensive, the main, and commonly only, treatment option remains liver transplantation. Dietary manipulation is an approach of high interest to patients. Presumably, diet may have some influence on the intestinal microbiome and have a modifying impact on the diseases but this has not been well established.

The investigators propose a study period of approximately 14 weeks to evaluate the effects of the SCD and vegan/low-sulfur diet on the intestinal microbiome and bile acid composition in stool and serum. Patients will visit their study site or participate in a video visit 7 times over the course of the study. At the screening visit (Week 0), eligibility will be assessed, lab tests will be performed, and subjects will be randomized to dietary instruction on one of the two diets with educational materials, recipes, and food procurement stipend provided. Consent will be signed at or before the screening visit either in-person or remotely. Patients will be asked to collect a stool sample and complete a Food Frequency Questionnaire (FFQ).

The treatment phase of 8 weeks will begin at the baseline visit (Week 2). At each of the four time points during the treatment phase (Week 4, 6, 8, 10), participants will record in real-time what they eat by a smartphone app for 3-days, one of which includes a weekend. To enhance compliance to the intervention protocol, the dedicated study coordinator along with the Registered Dietitian will review the food diary data in real-time and discuss any challenges to comply with the meal intervention. After the 8-week treatment period is complete, patients will be encouraged to continue with their diet, self-directed, for 4 weeks following the end of the treatment phase (Week 10). Subjects will be asked to return for one final visit at Week 14 to complete a 3-day food diary and have labs drawn.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Males and females between 18 and 70 years of age, inclusive based on the date of the screening visit

2. Willing and able to give informed consent prior to any study specific procedures being performed

3. Diagnosis of PSC documented by typical cholangiogram findings with no evidence of a secondary cause of sclerosing cholangitis

4. Serum alkaline phosphatase greater than 1.5 times the upper limit of the normal (ULN) reference range

5. Simple clinical colitis activity index < 5

6. For subjects on UDCA, the dose of UDCA must have been stable for at least 3 months before screening. For subjects not on UDCA, no UDCA use for at least 3 months before screening.

7. Platelet count > 150,000/mm3

8. Albumin > 3.3 g/dL

9. Serum creatinine < ULN

10. Willing and able to comply with scheduled visits, laboratory tests, stool collection, and other study procedures including to follow a vegan/low-sulfur diet or SCD for the duration of the trial regardless of treatment arm randomization

11. Able to read English and complete PSC PRO independently

Exclusion Criteria:

1. Pregnant or lactating females

2. ALT > 10 x ULN

3. Total bilirubin > 2 X ULN

4. INR > 1.2

5. Decompensated cirrhosis defined by ascites, hepatic encephalopathy, or variceal bleeding

6. Small duct PSC

7. Other causes of liver disease including secondary sclerosing cholangitis, viral, metabolic, alcoholic, and other autoimmune liver diseases. Subjects with non-alcoholic fatty liver disease may be included if there is no evidence of NASH in the opinion of the investigator

8. Positive AMA

9. History of liver transplantation

10. History of hepatocellular carcinoma or cholangiocarcinoma

11. Ascending cholangitis within 90 days of enrollment

12. Any antibiotic use within 90 days of enrollment or planned antibiotic use during the study period

13. Current vegetarian or adherence to the SCD

14. Nut allergy (Many of the recipes included in the specific carbohydrate diet substitute nut flour for wheat flour. Subjects randomized to either the specific carbohydrate diet arm will have difficulty with dietary adherence as they will be intolerant of this dietary staple).

15. Inability to complete dietary log.

16. History of malignancy within 5 years except for adequately treated carcinoma in situ of the cervix and basal or squamous cell carcinoma.

17. Concurrent participation in another therapeutic clinical trial

18. Celiac disease

19. Any laboratory abnormality or condition which in the opinion of the investigator could adversely affect the safety of the participant or impair the assessment of the study results

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Other:
• Dietary Intervention
Subjects will be placed on 1 of 2 diets for a treatment period of 8 weeks with the support of dietitians; it will then be evaluated whether they can continue this diet on their own for 4 weeks.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Massachusetts General Hospital, University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Shannon index	The primary endpoint will be the within group change in the Shannon diversity index. The Shannon diversity index is used to characterize species diversity in a community (the diversity in the fecal microbiome).	Control period (Weeks 0-2) to Week 14
Secondary	ALP level	The investigators will be evaluating the trend of alkaline phosphatase reduction (U/L).	Control period (Weeks 0-2) to Week 14