Ignite Creation Date:
2025-12-24 @ 2:35 PM
Ignite Modification Date:
2026-01-01 @ 4:55 PM
Study NCT ID:
NCT01171859
Status:
COMPLETED
Last Update Posted:
2016-02-25
First Post:
2010-07-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety, Efficacy and Pharmacokinetics of Doxycycline Plus Tauroursodeoxycholic Acid in Transthyretin Amyloidosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'C567782', 'term': 'Amyloidosis, Hereditary, Transthyretin-Related'}, {'id': 'D000686', 'term': 'Amyloidosis'}], 'ancestors': [{'id': 'D057165', 'term': 'Proteostasis Deficiencies'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D004318', 'term': 'Doxycycline'}, {'id': 'C031655', 'term': 'ursodoxicoltaurine'}], 'ancestors': [{'id': 'D013754', 'term': 'Tetracyclines'}, {'id': 'D009279', 'term': 'Naphthacenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-02', 'completionDateStruct': {'date': '2015-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-02-24', 'studyFirstSubmitDate': '2010-07-27', 'studyFirstSubmitQcDate': '2010-07-28', 'lastUpdatePostDateStruct': {'date': '2016-02-25', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2010-07-29', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Response rate to doxycycline + tauroursodeoxycholic acid treatment', 'timeFrame': 'One year', 'description': 'A responder is a subject with:\n\n* 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);\n* 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).'}], 'secondaryOutcomes': [{'measure': 'Number of patients experiencing treatment-emergent adverse events', 'timeFrame': 'One year'}, {'measure': 'Change in quality of life', 'timeFrame': 'Every six months', 'description': 'SF-36 scale'}, {'measure': 'doxycycline pharmacokinetics (PK)', 'timeFrame': 'Every three months'}, {'measure': 'response in autonomic dysfunction, sensory-motor peripheral neuropathy and visceral organ involvement', 'timeFrame': 'One year', 'description': 'response assessed according to the Kumamoto Scale score'}, {'measure': 'neurologic response', 'timeFrame': 'One year', 'description': 'response assessed by motor and sensory nerves conduction studies'}, {'measure': 'Incidence of patients discontinuing from the study because of clinical or laboratory adverse events', 'timeFrame': 'One year'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['amyloidosis', 'transthyretin', 'doxycycline', 'Tauroursodeoxycholic acid'], 'conditions': ['Transthyretin Amyloidosis']}, 'referencesModule': {'references': [{'pmid': '16449795', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '18572024', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '20673327', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nIt is a phase II, therapeutic exploratory, two-part, 18-month, single centre, prospective study.\n\nPart 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens;\n* Molecular definition of the transthyretin (TTR) mutation or immunohistochemical staining of amyloid fibrils with anti-TTR antibody;\n* ECOG performance status (PS) 0, 1, 2;\n* New York Heart Association (NYHA) class ≤III\n* Systolic blood pressure ≥100 mmHg (standing)\n* 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.\n* 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.\n\nExclusion Criteria:\n\n* Liver transplantation in the previous 12 months or liver transplantation anticipated in less than 6 months;\n* ALT and/or AST ≥ 2 x Upper Normal Limit (UNL);\n* Alkaline phosphatase ≥ 2 x UNL;\n* Creatinine clearance \\< 30 ml/min;\n* Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study;\n* Echocardiographic ejection fraction \\< 50%;\n* Other neuropathies, due to vitamin B12 deficiency, alcoholism, hypothyroidism, uremia, diabetes mellitus, vasculitides;\n* History of poor compliance;\n* History of hypersensitivity to any of the ingredients of the study therapies;\n* Use of any investigational drug, device (or biologic) within 4 weeks prior to study entry or during the study.'}, 'identificationModule': {'nctId': 'NCT01171859', 'briefTitle': 'Safety, Efficacy and Pharmacokinetics of Doxycycline Plus Tauroursodeoxycholic Acid in Transthyretin Amyloidosis', 'organization': {'class': 'OTHER', 'fullName': 'Fondazione IRCCS Policlinico San Matteo di Pavia'}, 'officialTitle': 'A Single Center, Twelve-month, Open-label, Prospective Study Followed by a Six-month Withdrawal Period to Evaluate the Efficacy, Tolerability, Safety and Pharmacokinetics of Doxycycline in Combination With Tauroursodeoxycholic Acid in Transthyretin Amyloidosis', 'orgStudyIdInfo': {'id': 'DOXYTUDCA2010'}, 'secondaryIdInfos': [{'id': '2010-020422-17', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Doxycycline + Tauroursodeoxycholic acid', 'interventionNames': ['Drug: Doxycycline + Tauroursodeoxycholic acid']}], 'interventions': [{'name': 'Doxycycline + Tauroursodeoxycholic acid', 'type': 'DRUG', 'description': 'doxycycline 100 mg twice a day for 12 months; tauroursodeoxycholic acid 250 mg three times a day for 12 months', 'armGroupLabels': ['Doxycycline + Tauroursodeoxycholic acid']}]}, 'contactsLocationsModule': {'locations': [{'zip': '27100', 'city': 'Pavia', 'state': 'Pavia', 'country': 'Italy', 'facility': 'Amyloid Research and Treatment Centre, Biotechnology Research Laboratories', 'geoPoint': {'lat': 45.19205, 'lon': 9.15917}}], 'overallOfficials': [{'name': 'Giampaolo Merlini, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'IRCCS Policlinico San Matteo'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fondazione IRCCS Policlinico San Matteo di Pavia', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Prof.', 'investigatorFullName': 'Giampaolo Merlini', 'investigatorAffiliation': 'Fondazione IRCCS Policlinico San Matteo di Pavia'}}}}