NCT03591757

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

Completed EARLY_PHASE1 Last updated 14 June 2019

What this trial tests

EARLY_PHASE1 trial testing Tolcapone in Transthyretin Amyloidosis in 10 participants. Completed in 26 April 2019.

Timeline

30 October 2018

Primary endpoint
26 April 2019

26 April 2019

Quick facts

Lead sponsor	Boston University
Phase	EARLY_PHASE1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	30 October 2018
Primary completion	26 April 2019
Estimated completion	26 April 2019
Sites	1 location across United States

Drugs / interventions tested

• Tolcapone — full drug profile →

Conditions studied

• Transthyretin Amyloidosis — all drugs for Transthyretin Amyloidosis →
• Amyloidosis, Leptomeningeal, Transthyretin-Related — all drugs for Amyloidosis, Leptomeningeal, Transthyretin-Related →

Sponsor

Boston University

Who can join

18 and older, any sex, with Transthyretin Amyloidosis or Amyloidosis, Leptomeningeal, Transthyretin-Related. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Amyloidosis-the Diagnosis and Treatment of an Underdiagnosed Disease.
   Ihne S, Morbach C, Sommer C, Geier A, et al · · 2020 · cited 50× · PMID 32295695 · DOI 10.3238/arztebl.2020.0159
2. Treatment of Transthyretin Amyloid Cardiomyopathy: The Current Options, the Future, and the Challenges.
   Tschöpe C, Elsanhoury A. · · 2022 · cited 43× · PMID 35456241 · DOI 10.3390/jcm11082148
3. Treating Protein Misfolding Diseases: Therapeutic Successes Against Systemic Amyloidoses.
   Nevone A, Merlini G, Nuvolone M. · · 2020 · cited 26× · PMID 32754033 · DOI 10.3389/fphar.2020.01024