Primary Sclerosing CholangitisPhase 1NCT00325013
Evaluation of DHA for the Treatment of PSC
A Phase 1 study testing Docosahexaenoic Acid (DHA) in people with Primary Sclerosing Cholangitis and Colitis, run by Beth Israel Deaconess Medical Center at 2 sites in United States.
Trial summary
The researches aim to study the effects of DHA (component of fish oil) on patients with Primary Sclerosing Cholangitis (PSC). Our hypothesis is that DHA might reverse the problems associated with PSC. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Primary Sclerosing Cholangitis, Colitis
- What is being tested?
- Docosahexaenoic Acid (DHA)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2005to May 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a diagnosis of primary sclerosing cholangitis. The diagnosis will require a chronic cholestatic liver disease of at least 6 months' duration; a serum alkaline phosphatase level at least 1.5 times the upper limit of normal; cholangiographic findings of intrahepatic or extrahepatic biliary-duct obstruction, beading, or narrowing consistent with PSC; and a liver biopsy in the previous 12 months with compatible findings.
Who cannot join
- Age less than18 years or more than 80 years. Subjects must have no evidence of secondary cholangitis or other liver disease (primary biliary cirrhosis, alcoholic liver disease, autoimmune hepatitis, and chronic viral hepatitis). Subjects will be excluded if there is a history of previous bile duct surgery, previous choledocholithiasis, recurrent ascending cholangitis, previous history of variceal hemorrhage, or cholangiocarcinoma. Subjects with PSC stage III (fibrosis) or IV (cirrhosis) based on the criteria of Ludwig et al. will be excluded.
- Participants will be excluded if there are pregnant.
- Subjects will also be excluded if treatment with corticosteroids, cyclosporine or methotrexate has occurred within the preceding 3 months, or there is an anticipated need for liver transplantation within 1 year. No fish oil supplements will otherwise be allowed. Patients on 5-aminosalicylate preparations or azathioprine will remain on these preparations for the duration of the trial. Treatment with ursodeoxycholic acid will not be an exclusion criteria. Patients on this therapy will be advised to continue the drug throughout the trial. Those not on ursodeoxycholic acid will not be allowed to start this drug since it is could affect the alkaline phosphatase levels and is not an accepted efficacious therapy. Subjects will not be excluded for refusal of follow-up MRCP at study completion. There will be no exclusion based on sex, race, and ethnic background.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: Evaluation of Docosahexaenoic Acid (DHA) for the Treatment of Primary Sclerosing Cholangitis (PSC)
The researches aim to study the effects of DHA (component of fish oil) on patients with Primary Sclerosing Cholangitis (PSC). Our hypothesis is that DHA might reverse the problems associated with PSC.
Read the detailed description
The etiology of Primary Sclerosing Cholangitis (PSC) is unknown. There are no proven effective therapies and no early markers of the disease to predict which patients with colitis may be at risk to develop PSC.
Our group has demonstrated an increased prevalence of CFTR alleles (the gene responsible for Cystic Fibrosis (CF)) in patients with PSC which was correlated with decreased CFTR function as measured by Nasal Potential Difference Testing. These data suggested that colitis in the setting of CFTR dysfunction may lead to bile duct inflammation and fibrosis. As proof of concept, we subsequently demonstrated in cftr-/- mice that (1) colitis leads to the development of bile duct injury and (2) this is prevented by correction of the CFTR related fatty acid defect with oral Docosahexaenoic Acid (DHA). Preliminary data in these mice indicates that low PPAR expression in the liver may predispose to inflammation. One mechanism by which DHA ameliorates the innate inflammatory response linked to CFTR dysfunction may be through an increase in PPAR expression.
Based on these data, we hypothesize that CFTR dysfunction may contribute to the pathogenesis of primary sclerosing cholangitis (PSC). Furthermore, correction of the fatty acid abnormality and changes in the innate immune response associated with CFTR dysfunction by oral administration of docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, might be an effective therapy for patients with PSC.
Immediate Objectives:
To evaluate the effect of DHA therapy on patients with PSC, examining:
Primary Outcome:
- serum alkaline phosphatase
Secondary Outcomes:
- cholangiography
- liver biochemistry (ALT, AST, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time,)
- fatty acid profile (docosahexaenoic acid, arachidonic acid)
- serum/plasma liver fibrosis markers (hyaluronic acid, tumor necrosis factor-α, transforming growth factor-ß, type III procollagen peptide)
- innate immune response (peripheral blood monocytes for assessment of cytokine secretion, lipoxins, and PPAR)
- clinical data on signs and symptoms
- Conditions
- Primary Sclerosing Cholangitis, Colitis
- Being tested
- Docosahexaenoic Acid (DHA)
- Keywords
- Primary Sclerosing Cholangitis, PSC, DHA, Docosahexaenoic Acid
- Medical subject headings
- Cholangitis, Sclerosing, Colitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Docosahexaenoic Acid (DHA)Drug
Also called fish oil
800mg twice a day for 1 year
| Study group | Role | What they receive |
|---|---|---|
| II | Experimental | Not described Receives: Drug: Docosahexaenoic Acid (DHA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary outcome will be change in alkaline phosphatase. Outcome in alkaline phosphatase will be defined as:Highly positive: >50% reduction;Positive: >25% reduction;
Measured: 1 years
No Change: <25% reduction or <25% increase;Negative: >25% increase;Highly negative: >50% increase
Measured: 1 years
Secondary outcomes (3)
Secondary outcomes will include changes in:cholangiography;liver biochemistry (ALT, AST, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time);fatty acid profile (docosahexaenoic acid, arachidonic acid);
Measured: 1 years
serum/plasma liver fibrosis markers (hyaluronic acid, tumor necrosis factor-α, transforming growth factor-ß, type III procollagen peptide);peripheral blood monocyte PPAR (mRNA by RT-PCR, protein level by western blot, and activity by EMSA);
Measured: 1 year
peripheral blood monocyte cytokine secretion (IL-8) in response to Pseudomonas LPS, TNF, IL-10; lipoxin A4 secretion and lipoxygenase expression as well as docosatriene/resolvins;symptoms;safety measures of DHA (Adverse Event recordings)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2006 (estimated)
- Study startDec 2005
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Sclerosing CholangitisStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven Freedman, Beth Israel Deaconess Medical Center
- Investigators
- Steve D Freedman, MD, PhD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00325013
- Sponsor's protocol ID
- 2005P-000259 (DK71851)
- Other IDs
- R03DK071851
- Status last verified
- Mar 2015
- First submitted
- 10 May 2006
- Last updated
- 11 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Docosahexaenoic Acid (DHA) for the Treatment of Primary Sclerosing Cholangitis (PSC)
- ClinicalTrials.gov ID
- NCT00325013
- Acronym / sponsor ID
- 2005P-000259 (DK71851)
- Conditions
- Primary Sclerosing Cholangitis, Colitis
- Keywords
- Primary Sclerosing Cholangitis, PSC, DHA, Docosahexaenoic Acid
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Dec 2005
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 11 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The researches aim to study the effects of DHA (component of fish oil) on patients with Primary Sclerosing Cholangitis (PSC). Our hypothesis is that DHA might reverse the problems associated with PSC.
Detailed description
The etiology of Primary Sclerosing Cholangitis (PSC) is unknown. There are no proven effective therapies and no early markers of the disease to predict which patients with colitis may be at risk to develop PSC.
Our group has demonstrated an increased prevalence of CFTR alleles (the gene responsible for Cystic Fibrosis (CF)) in patients with PSC which was correlated with decreased CFTR function as measured by Nasal Potential Difference Testing. These data suggested that colitis in the setting of CFTR dysfunction may lead to bile duct inflammation and fibrosis. As proof of concept, we subsequently demonstrated in cftr-/- mice that (1) colitis leads to the development of bile duct injury and (2) this is prevented by correction of the CFTR related fatty acid defect with oral Docosahexaenoic Acid (DHA). Preliminary data in these mice indicates that low PPAR expression in the liver may predispose to inflammation. One mechanism by which DHA ameliorates the innate inflammatory response linked to CFTR dysfunction may be through an increase in PPAR expression.
Based on these data, we hypothesize that CFTR dysfunction may contribute to the pathogenesis of primary sclerosing cholangitis (PSC). Furthermore, correction of the fatty acid abnormality and changes in the innate immune response associated with CFTR dysfunction by oral administration of docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, might be an effective therapy for patients with PSC.
Immediate Objectives:
To evaluate the effect of DHA therapy on patients with PSC, examining:
Primary Outcome:
- serum alkaline phosphatase
Secondary Outcomes:
- cholangiography
- liver biochemistry (ALT, AST, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time,)
- fatty acid profile (docosahexaenoic acid, arachidonic acid)
- serum/plasma liver fibrosis markers (hyaluronic acid, tumor necrosis factor-α, transforming growth factor-ß, type III procollagen peptide)
- innate immune response (peripheral blood monocytes for assessment of cytokine secretion, lipoxins, and PPAR)
- clinical data on signs and symptoms
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| II | Experimental | Drug: Docosahexaenoic Acid (DHA) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients must have a diagnosis of primary sclerosing cholangitis. The diagnosis will require a chronic cholestatic liver disease of at least 6 months' duration; a serum alkaline phosphatase level at least 1.5 times the upper limit of normal; cholangiographic findings of intrahepatic or extrahepatic biliary-duct obstruction, beading, or narrowing consistent with PSC; and a liver biopsy in the previous 12 months with compatible findings.
Key exclusion criteria (3 listed)
- Age less than18 years or more than 80 years. Subjects must have no evidence of secondary cholangitis or other liver disease (primary biliary cirrhosis, alcoholic liver disease, autoimmune hepatitis, and chronic viral hepatitis). Subjects will be excluded if there is a history of previous bile duct surgery, previous choledocholithiasis, recurrent ascending cholangitis, previous history of variceal hemorrhage, or cholangiocarcinoma. Subjects with PSC stage III (fibrosis) or IV (cirrhosis) based on the criteria of Ludwig et al. will be excluded.
- Participants will be excluded if there are pregnant.
- Subjects will also be excluded if treatment with corticosteroids, cyclosporine or methotrexate has occurred within the preceding 3 months, or there is an anticipated need for liver transplantation within 1 year. No fish oil supplements will otherwise be allowed. Patients on 5-aminosalicylate preparations or azathioprine will remain on these preparations for the duration of the trial. Treatment with ursodeoxycholic acid will not be an exclusion criteria. Patients on this therapy will be advised to continue the drug throughout the trial. Those not on ursodeoxycholic acid will not be allowed to start this drug since it is could affect the alkaline phosphatase levels and is not an accepted efficacious therapy. Subjects will not be excluded for refusal of follow-up MRCP at study completion. There will be no exclusion based on sex, race, and ethnic background.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Docosahexaenoic Acid (DHA)Also: fish oil800mg twice a day for 1 year | Drug | II |
Primary outcome
Primary outcome will be change in alkaline phosphatase. Outcome in alkaline phosphatase will be defined as:Highly positive: >50% reduction;Positive: >25% reduction;
Time frame: 1 years
No Change: <25% reduction or <25% increase;Negative: >25% increase;Highly negative: >50% increase
Time frame: 1 years
3 secondary outcomes
Secondary outcomes will include changes in:cholangiography;liver biochemistry (ALT, AST, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time);fatty acid profile (docosahexaenoic acid, arachidonic acid);
Time frame: 1 years
serum/plasma liver fibrosis markers (hyaluronic acid, tumor necrosis factor-α, transforming growth factor-ß, type III procollagen peptide);peripheral blood monocyte PPAR (mRNA by RT-PCR, protein level by western blot, and activity by EMSA);
Time frame: 1 year
peripheral blood monocyte cytokine secretion (IL-8) in response to Pseudomonas LPS, TNF, IL-10; lipoxin A4 secretion and lipoxygenase expression as well as docosatriene/resolvins;symptoms;safety measures of DHA (Adverse Event recordings)
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steve D Freedman, MD, PhD principal investigator
Beth Israel Deaconess Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Docosahexaenoic Acid (DHA) in people with Primary Sclerosing Cholangitis and Colitis, run by Beth Israel Deaconess Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary outcome will be change in alkaline phosphatase. Outcome in alkaline phosphatase will be defined as:Highly positive: >50% reduction;Positive: >25% reduction; (time frame: 1 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2015.