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Safety and Effect of Doxycycline in Patients With Amyloidosis

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ClinicalTrials.gov Identifier: NCT01677286
Recruitment Status : Completed
First Posted : September 3, 2012
Results First Posted : June 6, 2017
Last Update Posted : August 1, 2017
Sponsor:
Information provided by (Responsible Party):
John L. Berk, Boston University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Amyloidosis
Intervention Drug: Doxycycline 100 mg po bid x 12 months
Enrollment 25
Recruitment Details Patients referred to an amyloidosis center and no longer requiring active treatment to control progressive disease were recruited to the study.
Pre-assignment Details  
Arm/Group Title Doxycycline 100 mg po Bid x 12 Months
Hide Arm/Group Description Open-label doxycycline 100 mg twice daily by mouth will be administered to subjects for 12 months.
Period Title: Overall Study
Started 25
Completed 14
Not Completed 11
Arm/Group Title Doxycycline 100 mg po Bid x 12 Months
Hide Arm/Group Description Open-label doxycycline 100 mg twice daily by mouth will be administered to subjects for 12 months.
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 25 participants
65
(36 to 82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
6
  24.0%
Male
19
  76.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 25 participants
24
  96.0%
Multiple Number Analyzed 25 participants
1
   4.0%
Not hispanic or latino Number Analyzed 25 participants
24
  96.0%
Unknown/not reported Number Analyzed 25 participants
1
   4.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 25 participants
25
 100.0%
Brain Natriuretic Peptide (BNP)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 12 participants
385  (294)
[1]
Measure Description: Study participants with predominant cardiac amyloid involvement.
[2]
Measure Analysis Population Description: 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   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 12 participants
0.11  (0.07)
[1]
Measure Description: Study participants with predominant cardiac amyloid involvement.
[2]
Measure Analysis Population Description: 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)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mL/min
Number Analyzed 10 participants
83.3  (36.5)
[1]
Measure Description: Study participants with predominant renal amyloid involvement.
[2]
Measure Analysis Population Description: 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)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  G/day
Number Analyzed 10 participants
5.99  (3.15)
[1]
Measure Description: Study participants with predominant renal amyloid involvement.
[2]
Measure Analysis Population Description: 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.
1.Primary Outcome
Title Amyloid Cardiomyopathy: BNP
Hide Description Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at end of study reported
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cardiomyopathy
Hide Arm/Group Description:
Patients with predominant amyloid involvement of the heart.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: pg/mL
883  (703)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cardiomyopathy
Comments BNP pg/mL, baseline versus end study values
Type of Statistical Test Other
Comments P-values and confidence intervals are not adjusted for multiple testing
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Mixed Models Analysis
Comments degrees of freedom = 12
Method of Estimation Estimation Parameter Mean outcome change
Estimated Value 171
Confidence Interval (2-Sided) 95%
14.1 to 328
Estimation Comments [Not Specified]
2.Primary Outcome
Title Amyloid Cardiomyopathy: Troponin I
Hide Description Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at change at end of study reported
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with predominant amyloid involvement of the heart.
Arm/Group Title Cardiomyopathy
Hide Arm/Group Description:
Patients with predominant amyloid involvement of the heart.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.15  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cardiomyopathy
Comments Troponin I ng/mL, baseline versus end study levels.
Type of Statistical Test Other
Comments P-values and confidence intervals are not adjusted for multiple testing
Statistical Test of Hypothesis P-Value 0.340
Comments [Not Specified]
Method Mixed Models Analysis
Comments degrees of freedom = 12
Method of Estimation Estimation Parameter Mean outcome change
Estimated Value 0.0072
Confidence Interval (2-Sided) 95%
-0.009 to 0.0234
Estimation Comments [Not Specified]
3.Primary Outcome
Title Amyloid Nephropathy: Creatinine Clearance
Hide Description 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
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Amyloid Nephropathy
Hide Arm/Group Description:
Patients with predominant amyloid kidney involvement at enrollment.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: ml/min
82.4  (48.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Amyloid Nephropathy
Comments Creatinine clearance, baseline versus end study levels.
Type of Statistical Test Other
Comments P-values and confidence intervals are not adjusted for multiple testing
Statistical Test of Hypothesis P-Value 0.017
Comments [Not Specified]
Method Mixed Models Analysis
Comments degrees of freedom = 10
Method of Estimation Estimation Parameter Change in outcome measure
Estimated Value -7.39
Confidence Interval (2-Sided) 95%
-13.12 to -1.67
Estimation Comments [Not Specified]
4.Primary Outcome
Title Amyloid Nephropathy: Proteinuria
Hide Description Patients with predominant amyloid kidney involvement at enrollment.
Time Frame Data were assessed at baseline, 6 and 12 months, with change at end of study reported
Hide Outcome Measure Data
Hide Analysis Population Description
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 data collected at baseline, 6 and 12 months.
Arm/Group Title Amyloid Nephropathy: Proteinuria (g/Day)
Hide Arm/Group Description:
Patients with predominant amyloid kidney involvement at enrollment.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: g/day
5.91  (3.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Amyloid Nephropathy: Proteinuria (g/Day)
Comments Proteinuria (g/24 hours), baseline versus end study levels.
Type of Statistical Test Other
Comments P-values and confidence intervals are not adjusted for multiple testing
Statistical Test of Hypothesis P-Value 0.603
Comments [Not Specified]
Method Mixed Models Analysis
Comments degrees of freedom = 10
Method of Estimation Estimation Parameter Change in outcome measure
Estimated Value 0.091
Confidence Interval (2-Sided) 95%
-0.285 to 0.466
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Doxycycline 100 mg po Bid x 12 Months
Hide Arm/Group Description Open-label doxycycline 100 mg twice daily by mouth was administered to subjects for 12 months, if tolerated.
All-Cause Mortality
Doxycycline 100 mg po Bid x 12 Months
Affected / at Risk (%)
Total   0/25 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Doxycycline 100 mg po Bid x 12 Months
Affected / at Risk (%) # Events
Total   12/25 (48.00%)    
Blood and lymphatic system disorders   
osteonecrosis *  1/25 (4.00%)  1
Deep vein thrombosis *  1/25 (4.00%)  1
Cardiac disorders   
Fluid overload  [1]  3/25 (12.00%)  4
Arrhythmia * [2]  1/25 (4.00%)  1
Gastrointestinal disorders   
Bloating  [3]  1/25 (4.00%)  1
Hernia *  1/25 (4.00%)  1
Infections and infestations   
Cytomegalovirus infection *  1/25 (4.00%)  1
Musculoskeletal and connective tissue disorders   
Hip disease *  2/25 (8.00%)  2
Renal and urinary disorders   
Urinary retention   1/25 (4.00%)  1
Skin and subcutaneous tissue disorders   
Sun hypersensitivity  [4]  1/25 (4.00%)  1
Skin cancer *  1/25 (4.00%)  1
Surgical and medical procedures   
Orthopedic issues *  2/25 (8.00%)  2
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
[1]
SOB, edema
[2]
Ventricular trachycardia
[3]
Abdominal distension
[4]
Burns/desquamation induced by sun hypersensitivity
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Doxycycline 100 mg po Bid x 12 Months
Affected / at Risk (%) # Events
Total   21/25 (84.00%)    
Gastrointestinal disorders   
GI disorder   9/25 (36.00%)  18
Infections and infestations   
Infection *  5/25 (20.00%)  8
Skin and subcutaneous tissue disorders   
Skin disruption   15/25 (60.00%)  21
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: John Berk, MD
Organization: Boston Medical Center
Phone: 617-638-4494
EMail: jberk@bu.edu
Publications:
Responsible Party: John L. Berk, Boston University
ClinicalTrials.gov Identifier: NCT01677286     History of Changes
Other Study ID Numbers: H-31546
First Submitted: August 21, 2012
First Posted: September 3, 2012
Results First Submitted: March 19, 2017
Results First Posted: June 6, 2017
Last Update Posted: August 1, 2017