DUAL: Doxycycline to Upgrade Organ Response in Light Chain (AL) Amyloidosis Trial

Sponsor
Medical College of Wisconsin (Other)
Overall Status
Completed
CT.gov ID
NCT02207556
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
32
Enrollment
1
Location
1
Arm
67.6
Actual Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief 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 effects).

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 1, 2014
Actual Primary Completion Date :
Jul 31, 2017
Actual Study Completion Date :
May 19, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Doxycycline

Doxycycline will be administered at dose of 100mg orally twice daily for 1 year.

Drug: Doxycycline
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.
Other Names:
  • Doxycycline monohydrate
  • Outcome Measures

    Primary Outcome Measures

    1. Hematologic Response [1 year]

      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.

    Secondary Outcome Measures

    1. Amyloid Organ Response [6 months and 1 year]

      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.

    2. Mortality [Baseline, 3 months, 6 months, 1 year]

      The number of living subjects will be determined at Baseline, 3 months, 6 months and 1 year

    3. Patient-reported Health Quality of Life [Baseline, 3, 6, 9 and 12 months]

      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.

    4. Patient-reported Mental Quality of Life [Baseline, 3, 6, 9 and 12 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Patients with biopsy proven AL amyloidosis.

    2. Patients ≥ 18 years of age are eligible.

    3. Patient must provide informed consent.

    4. 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.

    5. A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.

    6. 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.

    7. Creatinine clearance of >25 ml/min.

    Exclusion Criteria:
    1. Patients with severe malabsorption syndrome precluding absorption of oral agents will be excluded.

    2. Known intolerance or allergic reactions with doxycycline.

    3. Previous chemotherapy for AL amyloidosis.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Froedtert & Medical College of WisconsinMilwaukeeWisconsinUnited States53226

    Sponsors and Collaborators

    • Medical College of Wisconsin
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Anita D'Souza, MD, Medical College of Wisconsin

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Anita D'Souza, Assistant Professor, Medical College of Wisconsin
    ClinicalTrials.gov Identifier:
    NCT02207556
    Other Study ID Numbers:
    • 22850
    • KL2TR001438
    • K23HL141445
    • 86-004-26
    First Posted:
    Aug 4, 2014
    Last Update Posted:
    Jul 9, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Anita D'Souza, Assistant Professor, Medical College of Wisconsin
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsSubjects were stratified by the type of amyloidosis. Subjects with primarily organ-based disease were classified as Localized Disease), whereas subjects with hematologic disease were classified as Systematic Disease. Each population received the same intervention but assessment of the clinical outcomes used different classification categories.
    Pre-assignment Detail
    Arm/Group TitleDoxycycline (Localized Disease)Doxacycline (Systemic Disease)
    Arm/Group DescriptionDoxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.Doxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.
    Period Title: Overall Study
    STARTED725
    COMPLETED520
    NOT COMPLETED25

    Baseline Characteristics

    Arm/Group TitleDoxycycline (Localized Disease)Doxycycline (Systemic Disease)Total
    Arm/Group DescriptionDoxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.Doxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.Total of all reporting groups
    Overall Participants72532
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    42.9%
    16
    64%
    19
    59.4%
    >=65 years
    4
    57.1%
    9
    36%
    13
    40.6%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    61.3
    (10.6)
    65.5
    (11.4)
    62.5
    (10.5)
    Sex: Female, Male (Count of Participants)
    Female
    5
    71.4%
    9
    36%
    14
    43.8%
    Male
    2
    28.6%
    16
    64%
    18
    56.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    7
    100%
    25
    100%
    32
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    4
    16%
    4
    12.5%
    White
    7
    100%
    21
    84%
    28
    87.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    7
    100%
    25
    100%
    32
    100%

    Outcome Measures

    1. Primary Outcome
    TitleHematologic Response
    DescriptionThis 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.
    Time Frame1 year

    Outcome Measure Data

    Analysis Population Description
    Hematologic response is not relevant to subjects with localized disease. Subjects with localized disease were not included in this analysis. Five participants had expired by the 1 year time point
    Arm/Group TitleDoxycycline (Systemic Disease)
    Arm/Group DescriptionDoxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.
    Measure Participants25
    Complete Response (CR)
    6
    85.7%
    Partial Response (PR)
    3
    42.9%
    Very Good Partial Response (VGPR)
    11
    157.1%
    Expired at 1 year
    5
    71.4%
    2. Secondary Outcome
    TitleAmyloid Organ Response
    DescriptionThis 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.
    Time Frame6 months and 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleDoxycycline (6 Months)Doxycycline (1 Year)
    Arm/Group DescriptionDoxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.Doxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.
    Measure Participants2525
    Progressive Disease
    8
    114.3%
    3
    12%
    Stable Disease
    8
    114.3%
    8
    32%
    Response
    6
    85.7%
    9
    36%
    Expired
    3
    42.9%
    5
    20%
    3. Secondary Outcome
    TitleMortality
    DescriptionThe number of living subjects will be determined at Baseline, 3 months, 6 months and 1 year
    Time FrameBaseline, 3 months, 6 months, 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleDoxycycline (Localized Disease)Doxacycline (Systemic Disease)
    Arm/Group DescriptionDoxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.Doxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.
    Measure Participants625
    Baseline
    6
    85.7%
    25
    100%
    3 Months
    6
    85.7%
    23
    92%
    6 Months
    6
    85.7%
    22
    88%
    1 Year
    6
    85.7%
    20
    80%
    4. Secondary Outcome
    TitlePatient-reported Health Quality of Life
    DescriptionSubjects 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.
    Time FrameBaseline, 3, 6, 9 and 12 months

    Outcome Measure Data

    Analysis Population Description
    One subject in the Localized cohort withdrew consent prior to the 6-month visit. Five subjects in the Systemic Disease cohort expired during the course of the study; two subjects came off study; and one was lost to follow-up.
    Arm/Group TitleDoxycycline (Localized Disease)Doxacycline (Systemic Disease)
    Arm/Group DescriptionDoxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.Doxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.
    Measure Participants625
    Baseline
    46.1
    (9.4)
    40.9
    (0.3)
    3 Months
    51.1
    (8.8)
    40.2
    (0.4)
    6 Months
    48.3
    (6.3)
    40.6
    (0.4)
    9 Months
    48.9
    (8.0)
    41.7
    (0.5)
    12 Months
    49.4
    (7.7)
    44.3
    (0.4)
    5. Secondary Outcome
    TitlePatient-reported Mental Quality of Life
    DescriptionSubjects 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.
    Time FrameBaseline, 3, 6, 9 and 12 months

    Outcome Measure Data

    Analysis Population Description
    One subject in the Localized cohort withdrew consent prior to the 6-month visit. Five subjects in the Systemic Disease cohort expired during the course of the study; two subjects came off study; and one was lost to follow-up.
    Arm/Group TitleDoxycycline (Localized Disease)Doxacycline (Systemic Disease)
    Arm/Group DescriptionDoxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.Doxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.
    Measure Participants625
    Baseline
    52.1
    (10.4)
    47.9
    (0.6)
    3 Month
    51.4
    (10.0)
    46.0
    (0.5)
    6 Months
    51.2
    (9.0)
    46.4
    (0.5)
    9 Months
    52.6
    (11.9)
    46.7
    (0.5)
    12 Months
    50.7
    (10.2)
    50.6
    (0.6)

    Adverse Events

    Time Frame1 year
    Adverse Event Reporting Description Grade was determined using the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. Events graded as 4 or 5 were considered serious regardless of the standard criteria.
    Arm/Group TitleDoxycycline (Localized Disease)Doxycycline (Systemic Disease)
    Arm/Group DescriptionDoxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.Doxycycline will be administered at dose of 100mg orally twice daily for 1 year. Doxycycline: 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.
    All Cause Mortality
    Doxycycline (Localized Disease)Doxycycline (Systemic Disease)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/5 (0%) 5/25 (20%)
    Serious Adverse Events
    Doxycycline (Localized Disease)Doxycycline (Systemic Disease)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/5 (20%) 13/25 (52%)
    Blood and lymphatic system disorders
    Lymphocyte production decreased0/5 (0%) 07/25 (28%) 7
    Neutrophil Count Decreased0/5 (0%) 06/25 (24%) 6
    Platelet Count Decreased0/5 (0%) 010/25 (40%) 10
    White Blood Cell Count Decreased0/5 (0%) 05/25 (20%) 5
    Death in Hospice0/5 (0%) 01/25 (4%) 1
    Thrombosis of Vein of Lower Limb0/5 (0%) 01/25 (4%) 1
    Cardiac disorders
    Progressive cardiac amyloidosis0/5 (0%) 01/25 (4%) 1
    Natural Death0/5 (0%) 01/25 (4%) 1
    Gastrointestinal disorders
    Colitis0/5 (0%) 01/25 (4%) 1
    Hepatobiliary disorders
    Aspartate Aminotransferase Increased0/5 (0%) 01/25 (4%) 1
    Alanine Aminotransferase Increased0/5 (0%) 01/25 (4%) 1
    Infections and infestations
    Adenovirus Infection0/5 (0%) 01/25 (4%) 1
    Bacterial Sepsis0/5 (0%) 01/25 (4%) 1
    Metabolism and nutrition disorders
    Hyperuricemia0/5 (0%) 01/25 (4%) 1
    Renal and urinary disorders
    Chronic Kidney Disease0/5 (0%) 01/25 (4%) 1
    Respiratory, thoracic and mediastinal disorders
    Respiratory Failure0/5 (0%) 01/25 (4%) 1
    Skin and subcutaneous tissue disorders
    Drug-Induced Lupus1/5 (20%) 10/25 (0%) 0
    Other (Not Including Serious) Adverse Events
    Doxycycline (Localized Disease)Doxycycline (Systemic Disease)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total5/5 (100%) 24/25 (96%)
    Blood and lymphatic system disorders
    Anemia0/5 (0%) 015/25 (60%) 15
    Cardiac disorders
    Cardiac Tropinin T Increased1/5 (20%) 14/25 (16%) 4
    Tachycardia0/5 (0%) 09/25 (36%) 9
    Sinus Tachycardia0/5 (0%) 06/25 (24%) 6
    Left Atrium Enlarged0/5 (0%) 04/25 (16%) 4
    Palpitations0/5 (0%) 04/25 (16%) 4
    Chest Pain - Cardiac0/5 (0%) 03/25 (12%) 3
    Irregular Heartbeat0/5 (0%) 03/25 (12%) 3
    Right Atrium Enlarged0/5 (0%) 03/25 (12%) 3
    Bradycardia0/5 (0%) 02/25 (8%) 2
    Chest Tightness0/5 (0%) 02/25 (8%) 2
    Murmur, Systolic II/IV0/5 (0%) 02/25 (8%) 2
    Sinus Bradycardia0/5 (0%) 02/25 (8%) 2
    Ear and labyrinth disorders
    Hearing Impaired1/5 (20%) 10/25 (0%) 0
    Vertigo0/5 (0%) 02/25 (8%) 2
    Eye disorders
    Blurred Vison0/5 (0%) 03/25 (12%) 3
    Periorbital Edema/Puffiness0/5 (0%) 03/25 (12%) 3
    Cataract0/5 (0%) 02/25 (8%) 2
    Dry Eye0/5 (0%) 02/25 (8%) 2
    Eye Discharge0/5 (0%) 02/25 (8%) 2
    Photophobia0/5 (0%) 02/25 (8%) 2
    Watering Eyes0/5 (0%) 02/25 (8%) 2
    Gastrointestinal disorders
    Nausea2/5 (40%) 214/25 (56%) 14
    Diarrhea1/5 (20%) 115/25 (60%) 15
    Constipation0/5 (0%) 011/25 (44%) 11
    Abdominal Pain0/5 (0%) 010/25 (40%) 10
    Bloating0/5 (0%) 07/25 (28%) 7
    Dry Mouth0/5 (0%) 07/25 (28%) 7
    Dysphagia0/5 (0%) 06/25 (24%) 6
    Sore Throat0/5 (0%) 06/25 (24%) 6
    Vomiting0/5 (0%) 06/25 (24%) 6
    Hemorrhoids0/5 (0%) 04/25 (16%) 4
    Macroglossia0/5 (0%) 03/25 (12%) 3
    Mucocitis, Oral0/5 (0%) 03/25 (12%) 3
    Flatulence0/5 (0%) 02/25 (8%) 2
    General disorders
    Fatigue3/5 (60%) 315/25 (60%) 15
    Edema, Limb2/5 (40%) 215/25 (60%) 15
    Pain2/5 (40%) 28/25 (32%) 8
    Rib Pain1/5 (20%) 10/25 (0%) 0
    Fever0/5 (0%) 08/25 (32%) 8
    Noncardiac Chest Pain0/5 (0%) 07/25 (28%) 7
    Chills0/5 (0%) 05/25 (20%) 5
    Gait Disturbance, Unsteady0/5 (0%) 03/25 (12%) 3
    Edema, Tongue0/5 (0%) 02/25 (8%) 2
    Infections and infestations
    Upper Respiratory Infection2/5 (40%) 26/25 (24%) 6
    Rhinitis Infective1/5 (20%) 10/25 (0%) 0
    Streptococcal Test, Positive1/5 (20%) 10/25 (0%) 0
    Upper Respiratory Infection0/5 (0%) 06/25 (24%) 6
    Urinary Tract Infection0/5 (0%) 03/25 (12%) 3
    Thrush0/5 (0%) 02/25 (8%) 2
    Injury, poisoning and procedural complications
    Bruising2/5 (40%) 28/25 (32%) 8
    Fall1/5 (20%) 19/25 (36%) 9
    Sunburn (Burn)1/5 (20%) 10/25 (0%) 0
    Inguinal Hernia Repair0/5 (0%) 02/25 (8%) 2
    Injury to Lip0/5 (0%) 02/25 (8%) 2
    Skin Tear0/5 (0%) 02/25 (8%) 2
    Investigations
    Hypercalcemia2/5 (40%) 26/25 (24%) 6
    Hyperglycemia2/5 (40%) 217/25 (68%) 17
    Hyponatremia2/5 (40%) 216/25 (64%) 16
    Hyperkalemia1/5 (20%) 17/25 (28%) 7
    Hypoalbuminemia1/5 (20%) 115/25 (60%) 15
    Hypokalemia1/5 (20%) 114/25 (56%) 14
    Weight Gain1/5 (20%) 16/25 (24%) 6
    Weight Loss1/5 (20%) 116/25 (64%) 16
    Platelet Count Decreased0/5 (0%) 08/25 (32%) 8
    Lymphocyte Count Decreased1/5 (20%) 112/25 (48%) 12
    White Cell Count Decreased1/5 (20%) 110/25 (40%) 10
    Neutrophil Cound Decreased0/5 (0%) 06/25 (24%) 6
    AST Increased1/5 (20%) 18/25 (32%) 8
    ALT Increased1/5 (20%) 15/25 (20%) 5
    Creatinine Increased0/5 (0%) 010/25 (40%) 10
    Hypocalcemia0/5 (0%) 010/25 (40%) 10
    Alkaline Phosphatase Increased0/5 (0%) 07/25 (28%) 7
    Hyopohosphatemia0/5 (0%) 06/25 (24%) 6
    Hypomagnesemia0/5 (0%) 05/25 (20%) 5
    Bilirubin Increased0/5 (0%) 04/25 (16%) 4
    Hypermagnesemia0/5 (0%) 03/25 (12%) 3
    Hypernatremia0/5 (0%) 02/25 (8%) 2
    Hypoglycemia0/5 (0%) 02/25 (8%) 2
    Metabolism and nutrition disorders
    Hyperuricemia2/5 (40%) 20/25 (0%) 0
    Anorexia1/5 (20%) 111/25 (44%) 11
    Low Vitamin D1/5 (20%) 10/25 (0%) 0
    Hyperuricemia0/5 (0%) 08/25 (32%) 8
    Musculoskeletal and connective tissue disorders
    Arthralgia2/5 (40%) 25/25 (20%) 5
    Pain in extremity1/5 (20%) 111/25 (44%) 11
    Generalized Muscle Weakness0/5 (0%) 010/25 (40%) 10
    Back Pain0/5 (0%) 08/25 (32%) 8
    Stiffness0/5 (0%) 08/25 (32%) 8
    Neck Pain0/5 (0%) 04/25 (16%) 4
    Nervous system disorders
    Paresthesia1/5 (20%) 16/25 (24%) 6
    Dizziness0/5 (0%) 015/25 (60%) 15
    Dysgeusia0/5 (0%) 013/25 (52%) 13
    Peripheral Sensory Neuropathy0/5 (0%) 08/25 (32%) 8
    Headache0/5 (0%) 07/25 (28%) 7
    Akathisia0/5 (0%) 02/25 (8%) 2
    Hypersomnia0/5 (0%) 02/25 (8%) 2
    Psychiatric disorders
    Anxiety1/5 (20%) 18/25 (32%) 8
    Depression1/5 (20%) 14/25 (16%) 4
    Insomnia0/5 (0%) 013/25 (52%) 13
    Confusion0/5 (0%) 03/25 (12%) 3
    Renal and urinary disorders
    Nocturia1/5 (20%) 12/25 (8%) 2
    Urine Output Decreased1/5 (20%) 10/25 (0%) 0
    Urinary Frequency0/5 (0%) 07/25 (28%) 7
    Proteinuria0/5 (0%) 05/25 (20%) 5
    Hematuria0/5 (0%) 04/25 (16%) 4
    Acute Kidney Injury0/5 (0%) 03/25 (12%) 3
    Urinary Incontinence0/5 (0%) 02/25 (8%) 2
    Urinary Retention0/5 (0%) 02/25 (8%) 2
    Urinary Tract Pain0/5 (0%) 02/25 (8%) 2
    Urinary Urgency0/5 (0%) 02/25 (8%) 2
    Reproductive system and breast disorders
    Night Sweats0/5 (0%) 02/25 (8%) 2
    Respiratory, thoracic and mediastinal disorders
    Dyspnea2/5 (40%) 212/25 (48%) 12
    Tachypnea2/5 (40%) 26/25 (24%) 6
    Cough1/5 (20%) 112/25 (48%) 12
    Laryngeal Hemorrhage1/5 (20%) 10/25 (0%) 0
    Lung Crackles1/5 (20%) 10/25 (0%) 0
    Hypoxia0/5 (0%) 07/25 (28%) 7
    Nasal Congestion0/5 (0%) 07/25 (28%) 7
    Epistaxis0/5 (0%) 06/25 (24%) 6
    Wheezing0/5 (0%) 04/25 (16%) 4
    Hiccups0/5 (0%) 03/25 (12%) 3
    Pleural Effusion0/5 (0%) 02/25 (8%) 2
    Rales0/5 (0%) 02/25 (8%) 2
    Skin and subcutaneous tissue disorders
    Bullous Dermatitis1/5 (20%) 10/25 (0%) 0
    Contact Dermatitis1/5 (20%) 10/25 (0%) 0
    Dry Skin1/5 (20%) 17/25 (28%) 7
    Erythema0/5 (0%) 05/25 (20%) 5
    Purpura0/5 (0%) 04/25 (16%) 4
    Photosensitivity0/5 (0%) 03/25 (12%) 3
    Rash0/5 (0%) 03/25 (12%) 3
    Erythematous Rash0/5 (0%) 02/25 (8%) 2
    Petichial Rash0/5 (0%) 02/25 (8%) 2
    Ulceration, Skin0/5 (0%) 02/25 (8%) 2
    Vascular disorders
    Hypertension3/5 (60%) 36/25 (24%) 6
    Hypotension0/5 (0%) 011/25 (44%) 11
    Jugular Vein Distention0/5 (0%) 03/25 (12%) 3
    Cyanosis0/5 (0%) 02/25 (8%) 2
    Flushiing0/5 (0%) 02/25 (8%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE 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/TitleDr. Anita D'Souza
    OrganizationMedical College of Wisconsin
    Phone414-805-0637
    Emaildsouza@mcw.edu
    Responsible Party:
    Anita D'Souza, Assistant Professor, Medical College of Wisconsin
    ClinicalTrials.gov Identifier:
    NCT02207556
    Other Study ID Numbers:
    • 22850
    • KL2TR001438
    • K23HL141445
    • 86-004-26
    First Posted:
    Aug 4, 2014
    Last Update Posted:
    Jul 9, 2021
    Last Verified:
    Jun 1, 2021