IRB Number:

05-004296

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

Patients are being asked to participate in this research study because they have been diagnosed with Familial Amyloid Polyneuropathy (FAP) and have symptoms of nerve and/or heart damage. FAP is an inherited disease that attacks the nerves and heart, generally causing death 7-15 years after diagnosis. At present, the only treatment for FAP is liver transplantation.

Medicines are needed to treat this disease. A common anti-inflammatory drug called diflunisal (Dolobid) that is similar to Motrin has been shown to prevent amyloid formation in a test tube and in the blood of normal human volunteers. The research staff would like to find out if diflunisal stops amyloid production in patients with FAP. All patients participating in the study will be encouraged to seek liver transplantation. Patients pursuing liver transplantation will be welcomed into the study provided the operation is unlikely to be performed within 12 months of entering the study based on the status of the liver transplant waiting list. Participation in this study will not affect the patient's current status on a liver transplant waiting list, nor future listing for transplantation.

This research study is designed to establish whether diflunisal, an anti-inflammatory drug that has been used for over 20 years in patients with arthritis, can stop nerve and heart damage resulting from amyloid produced by patients with FAP. Researchers know that diflunisal prevents formation of amyloid in the test tube. This study will determine if diflunisal can block amyloid production in FAP patients.

Who is Eligible to Participate in the Study?

-Age 18 up to age 75 years old
-Diagnosed with Familial Amyloid Polyneuropathy (FAP) and have symptoms of nerve and/or heart damage

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

Before entering the study, patients will have a blood test for diabetes. Diabetes can damage nerves in ways similar to FAP, making it difficult to know which disease is causing the nerve problems. The researchers need to be sure that changes in how the patient's nerves work are due to FAP and not something else.

It is not clear at the present time whether it is better for patients with FAP to take diflunisal. For this reason, if agreeing to participate in this research study, whether patients receive diflunisal or an inactive pill (placebo) will be decided by randomization (similar to flipping a coin). The chances of the patient receiving either diflunisal or a placebo are approximately equal. Neither the patient nor their doctor will be able to choose which pills the patient receives.

Patients will receive either diflunisal (250 mg) or placebo pills twice daily for 24 months.

Although the diflunisal dose is low, the research staff will carefully monitor for kidney, liver or bone marrow complications of the drug by blood tests drawn at the following times: study entry, one, three, six, 12, 18, and 24 months after starting the drug. Four visits (study entry, six, 12, and 24 months) will take place at the study center with three visits at the patient's primary physician's office (one, three and 18 months). Results of blood tests obtained by the patient's Primary Care Physician will be faxed back to the study center on special forms.

Each study participant will be given a Patient Diary, which will help track their progress throughout the study. The research staff ask that the patient document events that may occur during their participation, and mail Diary Forms to the Study Site monthly.

The study is designed to determine whether diflunisal blocks nerve and/or heart disease progression in patients with FAP. All study participants will undergo extensive nerve testing and heart ultrasounds every 12 months (at study entry, 12 and 24 months). The neurological portion will include standard muscle strength testing, the speed at which electrical impulses move down nerves (nerve conduction velocity), and computer assessment of sensation in the legs and arms, as well as heart beat changes with deep breathing. To ensure reliable test results, these sophisticated nerve studies will be performed and repeated on two consecutive days at the beginning and end of the study. A second less technical nerve assessment (the Kumamoto Scale) will be based on an examination by a trained neurologist. None of these tests are experimental. Heart wall thickening and pump function will be assessed by echocardiogram. A general health questionnaire survey will be given to participants at study entry, 12 and 24 months. Modified body mass index (mBMI) will be calculated from the patient's height, weight, and serum albumin levels obtained with other clinical blood work at study entry, 12,and
24 months. Fat pad aspiration will also be performed at study entry, 12 and 24 months. A sample of fat cells from the wall of the patient's belly will be removed through a needle and tested to determine the amount of amyloid deposited.

Serum drug (diflunisal) levels and transthyretin stability testing will be performed at the study center visits (study entry, 6, 12 and 24 months) using blood drawn at the time of
clinical testing (no more than 3-5 teaspoons full). Unlike the clinical tests, the serum drug levels and stability testing are experimental. The patient's blood samples will be sent to a central laboratory at the Scripps Research Institute in La Jolla, California for the stability testing. Every patient entering the study will already have DNA (gene) testing to determine the diagnosis and type of familial amyloidosis. This information carries important implications for families, as familial amyloidosis is an inherited disease. Not all family members will have familial amyloidosis. Genetic counseling will be provided for all newly diagnosed patients and families requesting consultation.

How long will the Study run?

Patients will be in the study for two years.

Sponsor(s): Boston University

Study Activation/Registration Date: 10/27/2006

IRB Review and Approval Date: 07/07/2006

Study Type: Treatment

Projected Accrual: The plan is to have up to 200 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Peter J. Dyck, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 05/23/2008