ClinicalTrials.gov
ClinicalTrials.gov Menu

Lymphedema Study for Arm or Leg Lymphedema

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

August 25, 2014
October 7, 2014
July 19, 2018
September 14, 2018
September 14, 2018
March 2009
December 2016   (Final data collection date for primary outcome measure)
  • 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.
  • 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.
  • 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.
Amelioration of cutaneous histological architecture [ Time Frame: at 4 months ]
Change in cutaneous histological architecture noted by examination of skin punch biopsy samples, normal and lymphedema samples
Complete list of historical versions of study NCT02257970 on ClinicalTrials.gov Archive Site
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Bioimpedance readings [ Time Frame: at 4 months ]
If unilateral, a significant improvement in bioimpedance readings of the affected arm or leg compared to those of the normal arm or leg, at study end.
Not Provided
Limb volume [ Time Frame: at 4 months ]
Assessment of limb volume of the affected arm or leg at study end.
 
Lymphedema Study for Arm or Leg Lymphedema
Placebo-controlled, Case-controlled, Open Label Therapeutic Trial for Unilateral or Bilateral Lymphedema of Arm or Leg.
This study compares the effectiveness of a study drug versus placebo in the treatment of lymphedema.

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.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Lymphedema
  • Drug: Ketoprofen
  • Drug: Placebo
    Placebo to match ketoprofen.
  • Experimental: Part 1: Exploratory Group

    Ketoprofen 225-300 mgs daily, taken orally

    Ketoprofen-exploratory group: 225-300 mgs daily for four to six months

    Intervention: 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

    Intervention: 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

    Intervention: Drug: Placebo
  • 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

    Intervention: Drug: Ketoprofen
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
117
150
March 2017
December 2016   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 90 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT02257970
7781
No
Not Provided
Not Provided
Stanley Rockson, Stanford University
Stanford University
Not Provided
Principal Investigator: Stanley G Rockson, MD Stanford University
Stanford University
July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP