- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02257970
Lymphedema Study for Arm or Leg Lymphedema
Placebo-controlled, Case-controlled, Open Label Therapeutic Trial for Unilateral or Bilateral Lymphedema of Arm or Leg.
Study Overview
Detailed Description
Part 1 is feasibility, exploratory, open-label study of ketoprofen, to document effects.
Part 2, is open-label trial of ketoprofen to document histological response. Part 3 is double-blind randomized trial of receive placebo or ketoprofen to evaluate safety and efficacy.
We will try to determine how the study drug affects the body tissue by obtaining tissue biopsies (small pieces of skin from the arm or leg) before treatment and after treatment.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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California
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Stanford, California, United States, 94305
- Stanford University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- a history of lymphedema of one or more limbs (unilateral or bilateral), with a duration of > 6 months.
Exclusion Criteria:
- Patients with active cancer, infection or bleeding tendency will be excluded.
- We will also exclude patients with medical contraindications to NSAIDs, including history of allergies, know gastrointestinal intolerance, or other serious systemic illness (e.g., renal failure, hepatic dysfunction, congestive heart failure, neurological or psychological impairment) that would impair the patients' ability to participate.
- Minors (<18 years of age) *>90 years of age
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1: Exploratory Group
Ketoprofen 225-300 mgs daily, taken orally Ketoprofen-exploratory group: 225-300 mgs daily for four to six months |
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Experimental: Part 2: Open-label Group
Ketoprofen 225 mg daily, taken orally Open-label group: 75 mgs, three times daily, for four months |
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Placebo Comparator: Part 3: Placebo Group
Participants randomized to receive placebo: placebo, three times daily, taken orally Placebo: 1 capsule, three times daily, for four months |
Placebo to match ketoprofen.
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Active Comparator: Part 3: Ketoprofen Group
Participants randomized to receive active medication: ketoprofen 75 mgs., three times daily, taken orally Ketoprofen: 1 capsule, three times daily, for four months |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part 1: Count of Participants Able to Complete Ketoprofen Treatment
Time Frame: Baseline to month 6
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Participants who were able to complete ketoprofen treatment and experienced no treatment-related serious adverse events.
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Baseline to month 6
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Part 2: Change From Baseline in Cutaneous Histological Architecture
Time Frame: Baseline; Month 4
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Quantitative assessment of paired histological specimens of lymphedema skin pre- and post-treatment with ketoprofen.
The impact of treatment on cutaneous histopathology was evaluated through the use of an empirically-derived scoring system (comprised of dermal thickness, intercellular mucin content, deep dermal collagen content, and perivascular infiltrate); this quantitative assessment was developed and performed by a dermatopathologist.
Each characteristic was weighted equally and each specimen was assigned a cumulative subscale score of 0-5.
The scores were summed for a total score (range: 0-20) which is presented here.
Higher scores indicate a higher degree of pathology.
A quantitatively higher negative change indicates a more favorable therapeutic response in the histology.
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Baseline; Month 4
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Part 3: Measurement of Skin Thickness
Time Frame: Baseline and 4 months
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Caliper-measured skin thickness (mm) was serially assessed and pre-to-post paired analysis was performed for both arms (Placebo and Ketoprofen) of the study.
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Baseline and 4 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part 2: Measurement of Skin Thickness
Time Frame: Baseline and 4 months
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Caliper measured skin thickness (mm) of lymphedema-affected limb was serially assessed and pre-to-post paired analysis was performed.
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Baseline and 4 months
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Part 3: Change From Baseline in Cutaneous Histological Architecture
Time Frame: Baseline; 4 months
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Quantitative assessment of paired histological specimens of lymphedema skin pre- and post-treatment with ketoprofen or placebo, respectively.
The impact of treatment on cutaneous histopathology was evaluated through the use of an empirically-derived scoring system (comprised of dermal thickness, intercellular mucin content, deep dermal collagen content, and perivascular infiltrate); this quantitative assessment was developed and performed by a dermatopathologist.
Each characteristic was weighted equally and each specimen was assigned a cumulative subscale score of 0-5.
The scores were summed for a total score (range: 0-20) which is presented here.
Higher scores indicate a higher degree of pathology.
For the analysis, the 4-month post-minus-pre change in this score for ketoprofen- and placebo-recipients, respectively, was compared.
A quantitatively higher negative change indicates a more favorable therapeutic response in the histology.
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Baseline; 4 months
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Part 2/Part 3: Change From Baseline in Bioimpedance Spectroscopy
Time Frame: Baseline; 4 months
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A four-electrode configuration was used to non-invasively assess the extracellular and intracellular fluid contents of the limb.
Data were analyzed according to Cole theory, using the manufacturer's software (Impedimed Ltd.), to provide values for a bioimpedance ratio (Ro), the resistance of the extracellular fluid including lymph, R∞ the resistance of total tissue fluid and Ri, the resistance of the intracellular fluid.
For the purposes of these investigations, in patients with unilateral lymphedema, the ratio of Ro in the affected:unaffected limbs was analyzed in each patient, as a measure of the bioimpedance attributable to the extracellular fluid content.
An Ro level of 1.034 was considered normal; values ≥1.034 were considered abnormal.
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Baseline; 4 months
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Part 2/Part 3: Change in Limb Volume
Time Frame: Baseline; 4 months
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Quantitative assessment of limb volume (ml) of the affected limb at study end compared to pre-treatment values.
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Baseline; 4 months
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Part 3: Change in Systemic Inflammatory Mediator Granulocyte Colony Stimulating Factor (G-CSF)
Time Frame: Baseline; 4 months
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The systemic inflammatory response of G-CSF, in the two treatment groups, Ketoprofen and Placebo, will be assessed with Luminex-bead inflammasome analysis of pre- and post-treatment plasma samples.
G-CSF, a glycoprotein, is an inflammatory cytokine produced by endothelium and immune cells.
Ketoprofen is a unique NSAID possessing dual pathways of inflammatory inhibition, blocking cyclooxygenase (COX) and 5-LO.
Measurement using median fluorescence intensity (MFI) was employed.
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Baseline; 4 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Stanley G Rockson, MD, Stanford University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Lymphatic Diseases
- Lymphedema
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Ketoprofen
Other Study ID Numbers
- 7781
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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