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Lymphedema Study for Arm or Leg Lymphedema

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ClinicalTrials.gov Identifier: NCT02257970
Recruitment Status : Completed
First Posted : October 7, 2014
Results First Posted : September 14, 2018
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
Stanley Rockson, Stanford University

Brief Summary:
This study compares the effectiveness of a study drug versus placebo in the treatment of lymphedema.

Condition or disease Intervention/treatment Phase
Lymphedema Drug: Ketoprofen Drug: Placebo Phase 4

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 : Interventional  (Clinical Trial)
Actual Enrollment : 117 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Placebo-controlled, Case-controlled, Open Label Therapeutic Trial for Unilateral or Bilateral Lymphedema of Arm or Leg.
Study Start Date : March 2009
Actual Primary Completion Date : December 2016
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphedema
Drug Information available for: Ketoprofen

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

Drug: Ketoprofen
Experimental: Part 2: Open-label Group

Ketoprofen 225 mg daily, taken orally

Open-label group: 75 mgs, three times daily, for four months

Drug: Ketoprofen
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

Drug: Placebo
Placebo to match ketoprofen.

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

Drug: Ketoprofen



Primary Outcome Measures :
  1. Part 1: Count of Participants Able to Complete Ketoprofen Treatment [ Time Frame: Baseline to month 6 ]
    Participants who were able to complete ketoprofen treatment and experienced no treatment-related serious adverse events.

  2. Part 2: Change From Baseline in Cutaneous Histological Architecture [ Time Frame: Baseline; Month 4 ]
    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.

  3. Part 3: Measurement of Skin Thickness [ Time Frame: Baseline and 4 months ]
    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.


Secondary Outcome Measures :
  1. Part 2: Measurement of Skin Thickness [ Time Frame: Baseline and 4 months ]
    Caliper measured skin thickness (mm) of lymphedema-affected limb was serially assessed and pre-to-post paired analysis was performed.

  2. Part 3: Change From Baseline in Cutaneous Histological Architecture [ Time Frame: Baseline; 4 months ]
    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.

  3. Part 2/Part 3: Change From Baseline in Bioimpedance Spectroscopy [ Time Frame: Baseline; 4 months ]
    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.

  4. Part 2/Part 3: Change in Limb Volume [ Time Frame: Baseline; 4 months ]
    Quantitative assessment of limb volume (ml) of the affected limb at study end compared to pre-treatment values.

  5. Part 3: Change in Systemic Inflammatory Mediator Granulocyte Colony Stimulating Factor (G-CSF) [ Time Frame: Baseline; 4 months ]
    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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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02257970


Locations
United States, California
Stanford University
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Stanley G Rockson, MD Stanford University

Additional Information:
Responsible Party: Stanley Rockson, Allan and Tina Neill Professor of Lymphatic Research and Medicine; Professor of Cardiovascular Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT02257970     History of Changes
Other Study ID Numbers: 7781
First Posted: October 7, 2014    Key Record Dates
Results First Posted: September 14, 2018
Last Update Posted: September 14, 2018
Last Verified: July 2018

Keywords provided by Stanley Rockson, Stanford University:
Lymphedema
edema
swelling

Additional relevant MeSH terms:
Lymphedema
Lymphatic Diseases
Ketoprofen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action