Primary Systemic AmyloidosisPhase 2DUALNCT02207556
Doxycycline to Upgrade Organ Response in Light Chain (AL) Amyloidosis Trial
A Phase 2 study testing Doxycycline in people with Primary Systemic Amyloidosis, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
In this study the investigators want to find out more about the addition of the antibiotic, doxycycline, to standard anti-amyloid therapy in people with amyloidosis. The investigators want to find out whether doxycycline improves the response to standard anti-amyloid therapy and whether it causes any problems (side… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Systemic Amyloidosis
- What is being tested?
- Doxycycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2014to 19 May 2020
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with biopsy proven AL amyloidosis.
- Patients ≥ 18 years of age are eligible.
- Patient must provide informed consent.
- All patients must have measurable amyloid organ involvement of a vital organ (eg. heart, liver, kidneys). Localized amyloidosis will also be eligible as long as the amyloid involvement is radiologically measurable.
- A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
- Patients who have previously been taking doxycycline will be eligible as long as there is no contraindication to stay on doxycycline 100 mg twice daily (BID) for 1 year in the opinion of the treating physician.
- Creatinine clearance of >25 ml/min.
Who cannot join
- Patients with severe malabsorption syndrome precluding absorption of oral agents will be excluded.
- Known intolerance or allergic reactions with doxycycline.
- Previous chemotherapy for AL amyloidosis.
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert & Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Doxycycline to Upgrade Organ Response in Light Chain (AL) Amyloidosis (DUAL) Trial: A Phase II Open Label Study of Oral Doxycycline Administered as an Adjunct to Plasma Cell Directed Therapy in Light Chain (AL) Amyloidosis
In this study the investigators want to find out more about the addition of the antibiotic, doxycycline, to standard anti-amyloid therapy in people with amyloidosis. The investigators want to find out whether doxycycline improves the response to standard anti-amyloid therapy and whether it causes any problems (side effects).
Read the detailed description
Organ response to anti-plasma cell therapy in AL amyloidosis tends to lags behind hematologic response as chemotherapy may not clear pre-formed organ amyloid. Doxycycline has been shown to have inhibitory effects on amyloid fibril formation as well as de-fibrillogenic effects and shown to be beneficial in in vitro, murine models and other preclinical studies. The investigators will prospectively evaluate the safety and efficacy of doxycycline in AL amyloidosis patients when used in conjunction with anti-plasma cell chemotherapy.
- Conditions
- Primary Systemic Amyloidosis
- Being tested
- Doxycycline
- Keywords
- AL amyloidosis, amyloidosis, light chain amyloidosis
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Also called Doxycycline monohydrate
Doxycycline will be continued until one of the following criteria is met:
- Patient has completed 1 year of doxycycline therapy
- Patient develops any grade 3-4 toxicity related to doxycycline use.
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline | Experimental | Doxycycline will be administered at dose of 100mg orally twice daily for 1 year. Receives: Drug: Doxycycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematologic Response
This measure will record the number of subjects for each grade of response to therapy for subjects with Systematic Disease (hematologic) only. Hematologic response will be determined as follows.
Complete response (CR) - Negative serum/urine immunofixation with normal Free Light Chain (FLC) ratio
Very Good Partial Response (VGPR)- Difference between involved and uninvolved FLCs (dFLC) < 40 mg/L
Partial Response (PR)- dFLC decrease > 50%
No Response (NR)- less then PR.
Measured: 1 year
Secondary outcomes (4)
Amyloid Organ Response
This measure is the number of subjects (systemic disease only) for each grade of response. Efficacy will be measured in heart, liver, or kidney.
Heart N-terminal (NT)-proBNP response >30% and > 300 ng/L decrease in patients with baseline NT-proBNP ≥650 ng/L (Patients with progressively worsening renal function cannot be scored for NT-proBNP progression).
Improvement by 2 New York Heart Association (NYHA) classes without an increase in diuretic use or in echocardiographic wall thickness ≥ 2 mm reduction in the interventricular septal thickness by echocardiogram or improvement of ejection fraction by ≥20%.
Liver
≥50% decrease in an initially elevated alkaline phosphatase level, or Decrease in liver size by at least 2 cm by ultrasound.
Kidney 50% reduction in 24-hour urine protein excretion (at least 0.5 g/day) without worsening of creatinine or creatinine clearance by 25% over baseline.
Soft Tissue RECIST criteria will be used.
Measured: 6 months and 1 year
Mortality
The number of living subjects will be determined at Baseline, 3 months, 6 months and 1 year
Measured: Baseline, 3 months, 6 months, 1 year
Patient-reported Health Quality of Life
Subjects will complete the Patient Reported Outcomes Measurement Information System Global Health instrument, a 10-item standardized patient-reported outcome measure that provides global ratings of physical function, fatigue, pain, emotional distress to report on common domains of health-related quality of life. The survey comprises a series of 5-response Likert-style questions. For each question, a low score indicates lesser or absent symptom or condition and higher indicates more severe symptom or condition (e.g., 1= None to 5=Very severe). Automated scoring produces a T-score for each domain. This measure reports the physical health score. T-scores for this domain range from 16.2 to 67.7. Higher scores indicate poorer physical health.
Measured: Baseline, 3, 6, 9 and 12 months
Patient-reported Mental Quality of Life
Subjects will complete the Patient Reported Outcomes Measurement Information System Global Health instrument, a 10-item standardized patient-reported outcome measure that provides global ratings of physical function, fatigue, pain, emotional distress to report on common domains of health-related quality of life. The survey comprises a series of 5-response Likert-style questions. For each question, a low score indicates lesser or absent symptom or condition and higher indicates more severe symptom or condition (e.g., 1= None to 5=Very severe). Automated scoring produces a T-score for each domain. This measure reports the mental health score. T-scores for this domain range from 21.2 to 67.6. Higher scores indicate poorer mental health.
Measured: Baseline, 3, 6, 9 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2014 (estimated)
- Study start1 Oct 2014
- Primary completion31 Jul 2017
- Study completion19 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Systemic AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Anita D'Souza, Medical College of Wisconsin
- Investigators
- Anita D'Souza, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02207556
- Sponsor's protocol ID
- 22850
- Other IDs
- KL2TR001438, K23HL141445, 86-004-26
- Acronym
- DUAL
- Status last verified
- Jun 2021
- First submitted
- 23 Jul 2014
- Last updated
- 9 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
D'Souza A, Szabo A, Flynn KE, Dhakal B, Chhabra S, Pasquini MC, Weihrauch D, Hari PN. Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial. EClinicalMedicine. 2020 Jun 5;23:100361. doi: 10.1016/j.eclinm.2020.100361. eCollection 2020 Jun.
PubMed 32529175