LymphedemaPhase 4NCT02257970
Lymphedema Study for Arm or Leg Lymphedema
A Phase 4 study testing Ketoprofen in people with Lymphedema, run by Stanford University at 1 site in United States.
Trial summary
This study compares the effectiveness of a study drug versus placebo in the treatment of lymphedema. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Lymphedema
- What is being tested?
- Ketoprofen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 117 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Mar 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- a history of lymphedema of one or more limbs (unilateral or bilateral), with a duration of > 6 months.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Lymphedema
- Being tested
- Ketoprofen, Placebo
- Keywords
- Lymphedema, edema, swelling
- Medical subject headings
- Lymphedema, Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetoprofenDrug
PlaceboDrug
Placebo to match ketoprofen.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Exploratory Group | Experimental | Ketoprofen 225-300 mgs daily, taken orally
Ketoprofen-exploratory group: 225-300 mgs daily for four to six months Receives: Drug: Ketoprofen |
| Part 2: Open-label Group | Experimental | Ketoprofen 225 mg daily, taken orally
Open-label group: 75 mgs, three times daily, for four months Receives: Drug: Ketoprofen |
| Part 3: Placebo Group | Placebo comparator | Participants randomized to receive placebo: placebo, three times daily, taken orally
Placebo: 1 capsule, three times daily, for four months Receives: Drug: Placebo |
| Part 3: Ketoprofen Group | Active comparator | Participants randomized to receive active medication: ketoprofen 75 mgs., three times daily, taken orally
Ketoprofen: 1 capsule, three times daily, for four months Receives: Drug: Ketoprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Count of Participants Able to Complete Ketoprofen Treatment
Participants who were able to complete ketoprofen treatment and experienced no treatment-related serious adverse events.
Measured: Baseline to month 6
Part 2: Change From Baseline in Cutaneous Histological Architecture
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.
Measured: Baseline; Month 4
Part 3: Measurement of Skin Thickness
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.
Measured: Baseline and 4 months
Secondary outcomes (5)
Part 2: Measurement of Skin Thickness
Caliper measured skin thickness (mm) of lymphedema-affected limb was serially assessed and pre-to-post paired analysis was performed.
Measured: Baseline and 4 months
Part 3: Change From Baseline in Cutaneous Histological Architecture
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.
Measured: Baseline; 4 months
Part 2/Part 3: Change From Baseline in Bioimpedance Spectroscopy
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.
Measured: Baseline; 4 months
Part 2/Part 3: Change in Limb Volume
Quantitative assessment of limb volume (ml) of the affected limb at study end compared to pre-treatment values.
Measured: Baseline; 4 months
Part 3: Change in Systemic Inflammatory Mediator Granulocyte Colony Stimulating Factor (G-CSF)
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.
Measured: Baseline; 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2014 (estimated)
- Study startMar 2009
- Primary completionDec 2016
- Study completionMar 2017
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 LymphedemaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stanley Rockson, Stanford University
- Investigators
- Stanley G Rockson, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02257970
- Sponsor's protocol ID
- 7781
- Status last verified
- Oct 2022
- First submitted
- 25 Aug 2014
- Last updated
- 27 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Rockson SG, Tian W, Jiang X, Kuznetsova T, Haddad F, Zampell J, Mehrara B, Sampson JP, Roche L, Kim J, Nicolls MR. Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema. JCI Insight. 2018 Oct 18;3(20):e123775. doi: 10.1172/jci.insight.123775.
PubMed 30333315
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo-controlled, Case-controlled, Open Label Therapeutic Trial for Unilateral or Bilateral Lymphedema of Arm or Leg.
- ClinicalTrials.gov ID
- NCT02257970
- Acronym / sponsor ID
- 7781
- Conditions
- Lymphedema
- Keywords
- Lymphedema, edema, swelling
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Dec 2016 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 7 Oct 2014 (estimated)
- Results
- Posted 14 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study compares the effectiveness of a study drug versus placebo in the treatment of lymphedema.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1: Exploratory Group | Experimental | Drug: KetoprofenKetoprofen 225-300 mgs daily, taken orally Ketoprofen-exploratory group: 225-300 mgs daily for four to six months |
| Part 2: Open-label Group | Experimental | Drug: KetoprofenKetoprofen 225 mg daily, taken orally Open-label group: 75 mgs, three times daily, for four months |
| Part 3: Placebo Group | Placebo comparator | Drug: PlaceboParticipants randomized to receive placebo: placebo, three times daily, taken orally Placebo: 1 capsule, three times daily, for four months |
| Part 3: Ketoprofen Group | Active comparator | Drug: KetoprofenParticipants randomized to receive active medication: ketoprofen 75 mgs., three times daily, taken orally Ketoprofen: 1 capsule, three times daily, for four months |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- a history of lymphedema of one or more limbs (unilateral or bilateral), with a duration of > 6 months.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketoprofen | Drug | Part 1: Exploratory Group, Part 2: Open-label Group, Part 3: Ketoprofen Group |
| PlaceboPlacebo to match ketoprofen. | Drug | Part 3: Placebo Group |
Primary outcome
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.
5 secondary outcomes
Part 2: Measurement of Skin Thickness
Time frame: Baseline and 4 months
Part 3: Change From Baseline in Cutaneous Histological Architecture
Time frame: Baseline; 4 months
Part 2/Part 3: Change From Baseline in Bioimpedance Spectroscopy
Time frame: Baseline; 4 months
Part 2/Part 3: Change in Limb Volume
Time frame: Baseline; 4 months
Part 3: Change in Systemic Inflammatory Mediator Granulocyte Colony Stimulating Factor (G-CSF)
Time frame: Baseline; 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30333315Rockson SG, Tian W, Jiang X, Kuznetsova T, Haddad F, Zampell J, Mehrara B, Sampson JP, Roche L, Kim J, Nicolls MR. Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema. JCI Insight. 2018 Oct 18;3(20):e123775. doi: 10.1172/jci.insight.123775.
- Stanford Health Care: Center for Lymphatic and Venous DisordersLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stanley G Rockson, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketoprofen in people with Lymphedema, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Count of Participants Able to Complete Ketoprofen Treatment (time frame: Baseline to month 6). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02257970, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2022.