NCT03481972

A Study of Doxycycline and Tauroursodeoxycholic Acid (Doxy/TUDCA) Plus Standard Supportive Therapy Versus Standard Supportive Therapy Alone in Cardiac Amyloidosis Caused by Transthyretin

Completed Phase 3 Last updated 11 July 2024

What this trial tests

Phase 3 trial testing Doxycycline and tauroursodeoxycholic acid in TTR Cardiac Amyloidosis in 102 participants. Completed in 22 June 2023.

Timeline

11 April 2018

Primary endpoint
18 January 2023

22 June 2023

Quick facts

Lead sponsor	Fondazione IRCCS Policlinico San Matteo di Pavia
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	102
Start date	11 April 2018
Primary completion	18 January 2023
Estimated completion	22 June 2023
Sites	1 location across Italy

Drugs / interventions tested

• Doxycycline and tauroursodeoxycholic acid — full drug profile →
• Standard of care

Conditions studied

• TTR Cardiac Amyloidosis — all drugs for TTR Cardiac Amyloidosis →

Sponsor

Fondazione IRCCS Policlinico San Matteo di Pavia

Who can join

18 and older, any sex, with TTR Cardiac Amyloidosis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Cardiac amyloidosis caused by transthyretin either mutated (in ATTRm amyloidosis) or wildtype (in ATTRwt, formerly senile, amyloidosis) is a rare disease but is diagnosed with increasing frequency thanks to the availability of non-invasive scintigraphy-based means. Cardiac ATTR amyloidosis is characterized by progressive heart failure with a median survival of less than 4 years, and there is no standard treatment for this disease. It was proved that the marketed antibiotic doxycycline (Doxy) disrupts amyloid fibrils in vitro and in animal models synergistically with tauroursodeoxycholic acid (TUDCA). Based on these pre-clinical data, a clinical trial of Doxy/TUDCA in ATTR Amyloidosis (NCT01171859) was conducted.

Treatment was well tolerated and was able to prevent progression of cardiac dysfunction.

Publications & conference data

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

1. Hereditary transthyretin amyloidosis overview.
   Manganelli F, Fabrizi GM, Luigetti M, Mandich P, et al · · 2022 · cited 78× · PMID 33188616 · DOI 10.1007/s10072-020-04889-2
2. 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
3. Clinical Presentation, Diagnosis and Treatment of TTR Amyloidosis.
   Kapoor M, Rossor AM, Laura M, Reilly MM. · · 2019 · cited 48× · PMID 30829617 · DOI 10.3233/jnd-180371
4. Sex differences in transthyretin cardiac amyloidosis.
   Aimo A, Panichella G, Garofalo M, Gasparini S, et al · · 2024 · cited 33× · PMID 37566193 · DOI 10.1007/s10741-023-10339-w
5. Monoclonal antibodies and amyloid removal as a therapeutic strategy for cardiac amyloidosis.
   Emdin M, Morfino P, Crosta L, Aimo A, et al · · 2023 · cited 26× · PMID 37091656 · DOI 10.1093/eurheartjsupp/suad079
6. Current and Emerging Therapies for Hereditary Transthyretin Amyloidosis: Strides Towards a Brighter Future.
   Obici L, Mussinelli R. · · 2021 · cited 17× · PMID 34850359 · DOI 10.1007/s13311-021-01154-y
7. Diagnosis and treatment of transthyretin-related amyloidosis cardiomyopathy.
   Teng C, Li P, Bae JY, Pan S, et al · · 2020 · cited 17× · PMID 32725834 · DOI 10.1002/clc.23434
8. Current Therapies and Future Horizons in Cardiac Amyloidosis Treatment.
   Vogel J, Carpinteiro A, Luedike P, Buehning F, et al · · 2024 · cited 13× · PMID 38809394 · DOI 10.1007/s11897-024-00669-7