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Short-term Effects of TOLCAPONE on Transthyretin Stability in Subjects With Leptomeningeal TTR Amyloidosis (ATTR)

NCT03591757 · Status: COMPLETED · Phase: EARLY_PHASE1 · Type: INTERVENTIONAL · Enrollment: 10

Last updated 2019-06-14

No results posted yet for this study

Summary

The purpose of this study is to determine whether Tolcapone crosses from the blood stream into the fluid around the brain and stabilizes the protein that makes leptomeningeal amyloid. Tolcapone is a commercially available generic drug that treats Parkinson's disease.

The Investigator plans to evaluate Tolcapone as a treatment for ATTR (Transthyretin Amyloidosis), a rare genetic disease often causing death within 5-15 years after diagnosis. ATTR is characterized by deposition of misfolded protein known as amyloid, in one or more organ systems (including the peripheral and autonomic nervous systems, the heart, the brain and the eyes). The age at which symptoms begin to develop varies widely ranging between 20 to 70 years old. ATTR is progressive, and some variants can have a fatal outcome within a few years of presentation. Treatment options include supportive and symptomatic care that may slow or stop progressive decline in functional state but do not alter the pathological process. Liver transplant can be performed in selected patients but is limited by organ supply, requires lifelong immunosuppression, and may be complicated by progressive heart and nerve amyloid deposition. Importantly, liver transplant does not alter the natural course of central nervous system amyloid disease. To date, no treatment for ATTR penetrates the CNS.

At present there is no FDA approved treatment for ATTR amyloidosis in the US. In Europe, Tafamidis has been approved for treatment of stage 1 ATTR-polyneuropathy since 2012. Tafamidis and Tolcapone bind to the thyroxine binding site of TTR (with different drug-transthyretin interactions) and in so doing stabilizes the tetrameric form of TTR, preventing dissociation and amyloid fibril formation The preclinical and clinical data from a variety of experimental systems support the therapeutic activity of TOLCAPONE in TTR mediated disease.

Conditions

  • Transthyretin Amyloidosis
  • Amyloidosis, Leptomeningeal, Transthyretin-Related

Interventions

DRUG

Tolcapone

Tolcapone will be administered at 300 mg/day (100mg TID) orally to participants for 14 days and then 600 mg/day (200 mg TID) orally to participants for 14 days (approximately 5 hours apart). Participants will initiate 200mg TID after blood collection on Day 14.

Sponsors & Collaborators

  • Corino Therapeutics, Inc.

    collaborator INDUSTRY

  • Boston University

    lead OTHER

Principal Investigators

  • John L Berk, MD · The Amyloidosis Center, BUSM

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-10-30
Primary Completion
2019-04-26
Completion
2019-04-26
FDA Drug
Yes

Countries

  • United States

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03591757 on ClinicalTrials.gov