Primary Sclerosing Cholangitis
Conditions
Keywords
PSC, Thalidomide
Brief summary
The purpose of this study is to determine the safety and benefit of Thalidomide with primary sclerosing cholangitis (PSC). This is a six month study.
Detailed description
At entry, patients will have a complete history and physical, blood tests, ultrasound, and will complete questionnaires. Eligible patients will take Thalidomide 400 mg once a day in the evening. Patients will start a dose of 100 mg per day for two weeks, increasing by 100 mg per day every two weeks to a maximum dose of 400 mg per day for 6 months. Patients will return at 6 months for an evaluation, blood tests and completion of questionnaires. Blood tests will be performed by mailed-in kits at 3 months. Patients will receive weekly phone calls for the first 2 months and bi-monthly thereafter.
Interventions
DRUGThalidomide
Titrate to 400 mg daily for 6 months
Sponsors
Celgene Corporation
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 72 Years
Healthy volunteers
No
Inclusion criteria
* Previous diagnosis of primary sclerosing cholangitis as defined by: serum alkaline phosphatase level greater than or equal to 1.5 times the upper limit of normal, negative serum antimitochondrial antibody test, cholangiography diagnostic of PSC without other etiology for biliary obstruction, and liver histology consistent with or diagnostic of PSC * Patients must give written informed consent. * Patients must be willing and able to comply with the most recent version of the FDA-mandated System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.®) program.
Exclusion criteria
* Pregnant and/or lactating female * Inability or unwillingness to practice contraceptive measures for the prevention of pregnancy * History of hypersensitivity reaction to thalidomide * Inability to provide consent * Findings suggestive of liver disease of other etiology such as primary biliary cirrhosis, chronic alcoholic liver disease, chronic hepatitis B and C infection, hemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency, autoimmune hepatitis, and cryptogenic liver disease * Anticipated need for liver transplantation in one year from decompensated chronic liver disease or recurrent variceal bleeding, spontaneous hepatic encephalopathy, or refractory ascites * Treatment with tacrolimus, cyclosporine, sirolimus, ursodeoxycholic acid, corticosteroids, colchicine, methotrexate, azathioprine, cyclosporine, chlorambucil, budesonide, pentoxifylline, nicotine, silymarin, vitamin E or pirfenidone in the preceding three months * History of peripheral neuropathy * Use of medications with significant drug-drug interactions with thalidomide * History of Human Immunodeficiency Virus (HIV) positive status or Acquired Immunodeficiency Syndrome (AIDS) * History of coexistent advanced malignancy * History of coexistent severe cardiovascular disease * History of coexistent severe renal disease * History of current excessive or recent (within 6 months) alcohol use * Any condition that, in the opinion of the investigators, would interfere with the patient's ability to complete the study safely or successfully * History of thrombolytic events. Combination use with corticosteroids increases risk of deep vein thrombosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase | 6 months, baseline | The primary outcome was the change in serum liver biochemical parameter levels after 6 months of thalidomide when compared to baseline values. This was to be analyzed using the nonparametric Wilcoxon signed rank test of significance. This was based on the non-normal distribution of serum hepatic biochemical parameters among patients with PSC and the continuous nature of these variables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Toxicity and Tolerability | 6 months | Overall toxicity and tolerability were to be measured by the number of patients with development of neuropathy, increased liver biochemistries, drowsiness, dizziness and orthostatic hypotension. |
| Mayo Risk Score | 6 months | The Mayo Risk Score estimates the survival probability of a patient with primary sclerosing cholangitis based on the following variables: age, bilirubin, albumin, AST and history of variceal bleeding. |
| Soluble Tumor Necrosis Factor - Alpha | 6 months, baseline | Assessment of effect from thalidomide on soluble tumor necrosis factor - alpha compared to baseline values were to be performed at study conclusion. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited between 4/6/2006 and 5/7/2009 at Mayo Clinic outpatient area.
Participants by arm
| Arm | Count |
|---|---|
| Thalidomide Patients with primary sclerosing cholangitis (PSC) who met with enrollment criteria were treated with 400 mg in the evening for a duration of 6 months | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Thalidomide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase
The primary outcome was the change in serum liver biochemical parameter levels after 6 months of thalidomide when compared to baseline values. This was to be analyzed using the nonparametric Wilcoxon signed rank test of significance. This was based on the non-normal distribution of serum hepatic biochemical parameters among patients with PSC and the continuous nature of these variables.
Time frame: 6 months, baseline
Population: Analysis was not performed because participant did not complete the study due to adverse events.
Secondary
Mayo Risk Score
The Mayo Risk Score estimates the survival probability of a patient with primary sclerosing cholangitis based on the following variables: age, bilirubin, albumin, AST and history of variceal bleeding.
Time frame: 6 months
Secondary
Overall Toxicity and Tolerability
Overall toxicity and tolerability were to be measured by the number of patients with development of neuropathy, increased liver biochemistries, drowsiness, dizziness and orthostatic hypotension.
Time frame: 6 months
Secondary
Soluble Tumor Necrosis Factor - Alpha
Assessment of effect from thalidomide on soluble tumor necrosis factor - alpha compared to baseline values were to be performed at study conclusion.
Time frame: 6 months, baseline