An 18 Month, Open Label Study of the Tolerability and Efficacy of a Combination of Doxycycline and Tauroursodeoxycholic Acid (TUDCA) in Patients With Transthyretin Amyloid Cardiomyopathy.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Brigham and Women's Hospital
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Changes in Strain Echocardiography
Study Overview
Brief Summary
The objective of the study is to determine whether the combination of the bile acid TUDCA, and doxycycline will slow the progression of familial and senile amyloidosis.
Detailed Description
Primary objectives The study is designed to prospectively evaluate the efficacy of doxycycline and TUDCA, prescribed together, on cardiac disease progression in patients with senile systemic amyloidosis or familial amyloidosis due to a TTR mutation. The definition of progression will be defined, primarily, by echocardiographic indices , as well as by serial cardiac biomarkers, specifically NT-proBNP.
. Echocardiographic details
. Standard parameters of wall thickness, chamber size, Doppler echocardiographic assessment of valvular function and diastolic function will be measured.
The primary endpoint is the response rate to doxycycline + TUDCA treatment at month 12 and 18, based upon echocardiographic findings. Since the precise echocardiographic findings will determine the definition of a responder, an approximate figure on which progression is based will be given here, based on our previous, preliminary data. A responder will be defined as a patient with echocardiographic evidence of stability of speckle strain parameters at 12 months of therapy with doxycycline/TUDCA. Based on our preliminary work, this is currently defined as a change in absolute longitudinal strain of < -2%, but the use of this parameter may alter slightly after the part 1 analysis.
Secondary endpoints
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Documented transthyretin cardiac amyloidosis by biopsy and staining using immunohistochemistry or mass spectrometry
- •Echocardiographic appearance of left ventricular wall thickness of 13mm or more in the absence of hypertensive heart disease
- •Confirmed ATTR or SSA by genetic testing
- •Age 18-90
- •Male or non-pregnant, non-lactating females
- •Willingness to return to the treatment center for follow-up
Exclusion Criteria
- •Prior liver transplantation or liver transplantation anticipated in less than 6 months
- •Alanine Transaminase and/or Aspartate Transaminase ≥2 x upper normal limit (UNL)
- •Alkaline Phosphatase ≥2 x UNL
- •Creatinine clearance <20 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
- •History of poor compliance
- •History of hypersensitivity to any of the ingredients of the study therapies
- •Any investigational drug within 4 weeks prior to study entry or during the study
- •Current use of diflunisal for therapy of amyloidosis
Arms & Interventions
TUDCA and Doxycycline
INTERVENTION: Patients meeting study criteria were prescribed TUDCA taken orally, 250 mg three times daily. and doxycycline taken orally, 100 mg twice daily.
Intervention: Tauroursodeoxycholic Acid and Doxycycline (Drug)
Outcomes
Primary Outcomes
Changes in Strain Echocardiography
Time Frame: Time Frame: * (FDAAA) outcome measure is assessed every 6 months by serial echocardiography, with final measurement 18 months after enrollment, change at 12 months reported as pre-defined primary endpoint.
Outcome measure, namely changes in longitudinal echocardiographic strain, will be compared to previously determined changes derived from a cohort of patients with TTR cardiac amyloidosis who were not receiving specific therapy for amyloid deposition.
Secondary Outcomes
- Number of Patients With Adverse Events(18 months)
Investigators
Rodney H. Falk, MD
Director, Brigham and Women's Hospital Cardiac Amyloidosis Program
Brigham and Women's Hospital