Trial Outcomes & Findings for Safety and Effect of Doxycycline in Patients With Amyloidosis (NCT NCT01677286)

NCT ID: NCT01677286

Last Updated: 2017-08-01

Results Overview

Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at end of study reported

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

12 months

Results posted on

2017-08-01

Participant Flow

Patients referred to an amyloidosis center and no longer requiring active treatment to control progressive disease were recruited to the study.

Participant milestones

Participant milestones
Measure	Doxycycline 100 mg po Bid x 12 Months Open-label doxycycline 100 mg twice daily by mouth will be administered to subjects for 12 months.
Overall Study STARTED	25
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Patients with predominant amyloid cardiomyopathy constituted the "cardiac group" (n=12). Serial cardiac biomarkers (BNP, Troponin I) determinations were used to assess the effect of doxycycline on cardiac amyloid disease progression.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Doxycycline 100 mg po Bid x 12 Months n=25 Participants Open-label doxycycline 100 mg twice daily by mouth will be administered to subjects for 12 months.
Age, Continuous	65 Years n=25 Participants
Sex: Female, Male Female	6 Participants n=25 Participants
Sex: Female, Male Male	19 Participants n=25 Participants
Race/Ethnicity, Customized White	24 Participants n=25 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=25 Participants
Race/Ethnicity, Customized Not hispanic or latino	24 Participants n=25 Participants
Race/Ethnicity, Customized Unknown/not reported	1 Participants n=25 Participants
Region of Enrollment United States	25 Participants n=25 Participants
Brain Natriuretic Peptide (BNP)	385 pg/mL STANDARD_DEVIATION 294 • n=12 Participants • Patients with predominant amyloid cardiomyopathy constituted the "cardiac group" (n=12). Serial cardiac biomarkers (BNP, Troponin I) determinations were used to assess the effect of doxycycline on cardiac amyloid disease progression.
Troponin I	0.11 ng/mL STANDARD_DEVIATION 0.07 • n=12 Participants • Patients with predominant amyloid cardiomyopathy constituted the "cardiac group" (n=12). Serial cardiac biomarkers (BNP, Troponin I) determinations were used to assess the effect of doxycycline on cardiac amyloid disease progression.
Creatinine Clearance (mL/min)	83.3 mL/min STANDARD_DEVIATION 36.5 • n=10 Participants • Patients with predominant amyloid nephropathy constituted the "renal group" (n=10). Serial creatinine clearance and proteinuria were used to assess the effect of doxycycline on renal amyloid disease progression.
Proteinuria (g/day)	5.99 g/day STANDARD_DEVIATION 3.15 • n=10 Participants • Patients with predominant amyloid nephropathy constituted the "renal group" (n=10). Serial creatinine clearance and proteinuria were used to assess the effect of doxycycline on renal amyloid disease progression.

PRIMARY outcome

Timeframe: 12 months

Population: Analysis is limited to the patients with predominant amyloid heart involvement at enrollment. Mixed models analyses of change from baseline levels of cardiac biomarkers (BNP, Troponin I) were performed to include all collected data.

Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at end of study reported

Outcome measures

Outcome measures
Measure	Cardiomyopathy n=12 Participants Patients with predominant amyloid involvement of the heart.
Amyloid Cardiomyopathy: BNP	883 pg/mL Standard Deviation 703

PRIMARY outcome

Timeframe: 12 months

Population: Patients with predominant amyloid involvement of the heart.

Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at change at end of study reported

Outcome measures

Outcome measures
Measure	Cardiomyopathy n=12 Participants Patients with predominant amyloid involvement of the heart.
Amyloid Cardiomyopathy: Troponin I	0.15 ng/mL Standard Deviation 0.07

PRIMARY outcome

Timeframe: 12 months

Population: Analysis is limited to the patients with predominant amyloid kidney involvement at enrollment. Mixed models analyses of change from baseline levels of creatinine clearance (ml/min) and proteinuria (g/day) were performed to include all collected data.

Creatinine clearance (ml/min) and proteinuria (g/day) were assessed at baseline, 6 and 12 months, with change at change at end of study reported

Outcome measures

Outcome measures
Measure	Cardiomyopathy n=10 Participants Patients with predominant amyloid involvement of the heart.
Amyloid Nephropathy: Creatinine Clearance	82.4 ml/min Standard Deviation 48.0

PRIMARY outcome

Timeframe: Data were assessed at baseline, 6 and 12 months, with change at end of study reported

Patients with predominant amyloid kidney involvement at enrollment.

Outcome measures

Outcome measures
Measure	Cardiomyopathy n=10 Participants Patients with predominant amyloid involvement of the heart.
Amyloid Nephropathy: Proteinuria	5.91 g/day Standard Deviation 3.85

Adverse Events

Doxycycline 100 mg po Bid x 12 Months

Serious events: 12 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Doxycycline 100 mg po Bid x 12 Months n=25 participants at risk Open-label doxycycline 100 mg twice daily by mouth was administered to subjects for 12 months, if tolerated.
Cardiac disorders Fluid overload	12.0% 3/25 • Number of events 4
Skin and subcutaneous tissue disorders Sun hypersensitivity	4.0% 1/25 • Number of events 1
Gastrointestinal disorders Bloating	4.0% 1/25 • Number of events 1
Renal and urinary disorders Urinary retention	4.0% 1/25 • Number of events 1
Blood and lymphatic system disorders osteonecrosis	4.0% 1/25 • Number of events 1
Surgical and medical procedures Orthopedic issues	8.0% 2/25 • Number of events 2
Blood and lymphatic system disorders Deep vein thrombosis	4.0% 1/25 • Number of events 1
Cardiac disorders Arrhythmia	4.0% 1/25 • Number of events 1
Musculoskeletal and connective tissue disorders Hip disease	8.0% 2/25 • Number of events 2
Infections and infestations Cytomegalovirus infection	4.0% 1/25 • Number of events 1
Skin and subcutaneous tissue disorders Skin cancer	4.0% 1/25 • Number of events 1
Gastrointestinal disorders Hernia	4.0% 1/25 • Number of events 1

Other adverse events

Other adverse events
Measure	Doxycycline 100 mg po Bid x 12 Months n=25 participants at risk Open-label doxycycline 100 mg twice daily by mouth was administered to subjects for 12 months, if tolerated.
Skin and subcutaneous tissue disorders Skin disruption	60.0% 15/25 • Number of events 21
Gastrointestinal disorders GI disorder	36.0% 9/25 • Number of events 18
Infections and infestations Infection	20.0% 5/25 • Number of events 8

Additional Information

John Berk, MD

Boston Medical Center

Phone: 617-638-4494

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place