CompletedNCT01171859Updated Feb 25, 2016

Safety, Efficacy and Pharmacokinetics of Doxycycline Plus Tauroursodeoxycholic Acid in Transthyretin Amyloidosis

A Phase 2 interventional study of Doxycycline + Tauroursodeoxycholic acid in Transthyretin Amyloidosis, sponsored by Fondazione IRCCS Policlinico San Matteo di Pavia. Completed at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-02-25.

Sponsored by Fondazione IRCCS Policlinico San Matteo di Pavia · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 40
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

This study is being conducted to explore the potential benefits of a twelve-month doxycycline (at the best tolerated dose of 200 mg/day) and tauroursodeoxycholic acid (750 mg/day) treatment on disease progression in patients affected by transthyretin amyloidosis, including: 1) patients not eligible for liver transplantation; 2) patients eligible for liver transplantation, as a "bridge" therapy between the time of diagnosis and surgery, with the aim of stabilizing the disease; 3) patients showing disease progression after liver transplantation performed since at least 1 year.

It is a phase II, therapeutic exploratory, two-part, 18-month, single centre, prospective study.

Part I is a 12-month, open label treatment period in which doxycycline (200 mg/day, continuously) and tauroursodeoxycholic acid (750 mg/day continuously) are administered to 40 consenting subjects with transthyretin amyloidosis. Part II is a withdrawal period in which subjects will be monitored for disease progression. During part I, subjects will be evaluated at baseline (study Day 0), and then after 3, 6, 9 and 12 months of doxycycline plus tauroursodeoxycholic acid treatment or at premature treatment discontinuation; during part II, they will be assessed at months 15 and 18. Monthly phone contacts and blood tests will be performed to monitor potential adverse events.

Conditions studied

Transthyretin Amyloidosis

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Keywords

amyloidosis
transthyretin
doxycycline
Tauroursodeoxycholic acid

In context

Amyloid Neuropathies, Familial

122 studies on the registry are indexed under Amyloid Neuropathies, Familial; 71 are open to participants now.

This study's enrollment of 40 is below the median of 60 across 61 interventional studies indexed under Amyloid Neuropathies, Familial.

Browse Amyloid Neuropathies, Familial studies →

Lead sponsor

Fondazione IRCCS Policlinico San Matteo di Pavia is the lead sponsor of 255 studies on the registry; 113 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens;
Molecular definition of the transthyretin (TTR) mutation or immunohistochemical staining of amyloid fibrils with anti-TTR antibody;
ECOG performance status (PS) 0, 1, 2;
New York Heart Association (NYHA) class ≤III
Systolic blood pressure ≥100 mmHg (standing)
Must have symptomatic organ involvement with amyloid to justify therapy; must have evidence of neuropathy and/or cardiomyopathy progression after liver transplantation performed since at least one year.
Contraception for women of childbearing potential. Medically approved contraception could include abstinence. A negative serum pregnancy test is required prior to initiation of treatment with study medication.

Exclusion criteria

Exclusion Criteria:

Liver transplantation in the previous 12 months or liver transplantation anticipated in less than 6 months;
ALT and/or AST ≥ 2 x Upper Normal Limit (UNL);
Alkaline phosphatase ≥ 2 x UNL;
Creatinine clearance \< 30 ml/min;
Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study;
Echocardiographic ejection fraction \< 50%;
Other neuropathies, due to vitamin B12 deficiency, alcoholism, hypothyroidism, uremia, diabetes mellitus, vasculitides;
History of poor compliance;
History of hypersensitivity to any of the ingredients of the study therapies;
Use of any investigational drug, device (or biologic) within 4 weeks prior to study entry or during the study.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 40 participants (actual)

Study arms

Experimental
Doxycycline + Tauroursodeoxycholic acid
Drug: Doxycycline + Tauroursodeoxycholic acid

Interventions

DrugDoxycycline + Tauroursodeoxycholic acid
doxycycline 100 mg twice a day for 12 months; tauroursodeoxycholic acid 250 mg three times a day for 12 months

What researchers measure

Primary outcomes

Response rate to doxycycline + tauroursodeoxycholic acid treatment
A responder is a subject with: * a modified body mass index (mBMI) reduction of less than 10% and a change in the Neurologic Impairment Score-Lower Limbs (NIS-LL) \<2 (in subjects with peripheral neuropathy); * a modified body mass index (mBMI) reduction of less than 10% and an increase in N-terminal natriuretic peptide type B (NT-proBNP) concentration of less than 30% or \< 300 pg/mL (in subjects with isolated cardiomyopathy).
Time frame: One year

Secondary outcomes

Number of patients experiencing treatment-emergent adverse events
Time frame: One year
Change in quality of life
SF-36 scale
Time frame: Every six months
doxycycline pharmacokinetics (PK)
Time frame: Every three months
response in autonomic dysfunction, sensory-motor peripheral neuropathy and visceral organ involvement
response assessed according to the Kumamoto Scale score
Time frame: One year
neurologic response
response assessed by motor and sensory nerves conduction studies
Time frame: One year
Incidence of patients discontinuing from the study because of clinical or laboratory adverse events
Time frame: One year

Study locations

1 site

Amyloid Research and Treatment Centre, Biotechnology Research Laboratories
Pavia, 27100, Italy

References and documents

Publications

Cardoso I, Saraiva MJ. Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. FASEB J. 2006 Feb;20(2):234-9. doi: 10.1096/fj.05-4509com. PubMed 16449795 ↗
Macedo B, Batista AR, Ferreira N, Almeida MR, Saraiva MJ. Anti-apoptotic treatment reduces transthyretin deposition in a transgenic mouse model of Familial Amyloidotic Polyneuropathy. Biochim Biophys Acta. 2008 Sep;1782(9):517-22. doi: 10.1016/j.bbadis.2008.05.005. Epub 2008 Jun 3. PubMed 18572024 ↗
Cardoso I, Martins D, Ribeiro T, Merlini G, Saraiva MJ. Synergy of combined doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models. J Transl Med. 2010 Jul 30;8:74. doi: 10.1186/1479-5876-8-74. PubMed 20673327 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 25, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01171859
Lead sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
Responsible party: Giampaolo Merlini (Prof., Fondazione IRCCS Policlinico San Matteo di Pavia) — Principal investigator
First posted: Jul 29, 2010
Start date: Jul 2010
Primary completion: Apr 2015
Completion: Oct 2015
Last update: Feb 25, 2016

Study contacts

Giampaolo Merlini, MD

principal investigator · IRCCS Policlinico San Matteo

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Feb 2016. You cannot join it, but the record below documents what was studied.

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