Characterization of Treatment Responses in Lymphedema

NCT03783715 | Terminated FDA Drug

• 1 other identifier: 49078
• Study Type: observational
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to investigate the treatment response of lymphedema, of the upper or lower extremity, during clinical, pharmacologic treatment of lymphedema with oral ketoprofen. Correlation of clinical responses (changes in limb volume and skin thickness) with changes in the inflammasome will help to define the molecular substrate of treatment response.

Conditions

Lymphedema

Outcome Measures

Primary Outcomes (1)

• Change in Systemic Inflammatory Mediator Granulocyte Colony Stimulating Factor (G-CSF)

  The systemic inflammatory response of G-CSF, in patients treated with Ketoprofen will be assessed with Luminex-bead inflammasome analysis at baseline and 6 months 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 arachidonate 5-lipoxygenase (5-LO). Measurement using median fluorescence intensity (MFI) will be employed.

  baseline and month 6.

Secondary Outcomes (2)

• Change in Measurement of Skin Thickness

  baseline and month 6.

• Change in Limb Volume

  baseline and month 6.

Study Arms (1)

Ketoprofen

Participants will take ketoprofen for six months. They will have evaluations at baseline and month 6.

Drug: Ketoprofen

Interventions

Ketoprofen DRUG

Ketoprofen 200 mg ER, taken orally, once a day for 6 months. If medication, if obtained from a compound pharmacy, dose will be 210 mg ER, taken orally once a day for 6 months.

Ketoprofen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients presenting to the Investigator's Stanford Center for Lymphatic and Venous Disorders, for evaluation and treatment of their condition, lymphedema, will be assessed for their suitability for medical treatment with ketoprofen. The use of ketoprofen in these patients is predicated upon clinical presentation and evidence-based practice, not any investigational consideration of therapy. If there are no contra-indications to taking ketoprofen, after discussion of FDA black box warnings, including provision of a written copy of the Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), approved by FDA, will be provided to the patient, and with the recommendation to discuss with the primary physician-of-record, patients will be provided with a prescription for ketoprofen. The opportunity to participate in this observational study will be presented.

You may qualify if:

• Participants with a history of acquired lymphedema
• Stage 1, 2, or 3
• years
• Clinical use of ketoprofen for lymphedema

You may not qualify if:

• Active cancer, infection, bleeding tendency, inflammatory disease and/or taking anti-inflammatory or anti-leukotriene medication will be excluded.
• Pregnant or lactating females
• Inability to take ketoprofen (contra-indicated, e.g patients with known CV, GI, renal, hepatic disease).
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, may interfere with interpretation of study results, and in the judgement of the investigator, would make the participation inappropriate for entry into this study.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (4)

• 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.

  PMID: 30333315 BACKGROUND

• Tian W, Rockson SG, Jiang X, Kim J, Begaye A, Shuffle EM, Tu AB, Cribb M, Nepiyushchikh Z, Feroze AH, Zamanian RT, Dhillon GS, Voelkel NF, Peters-Golden M, Kitajewski J, Dixon JB, Nicolls MR. Leukotriene B4 antagonism ameliorates experimental lymphedema. Sci Transl Med. 2017 May 10;9(389):eaal3920. doi: 10.1126/scitranslmed.aal3920.

  PMID: 28490670 BACKGROUND

• Nakamura K, Radhakrishnan K, Wong YM, Rockson SG. Anti-inflammatory pharmacotherapy with ketoprofen ameliorates experimental lymphatic vascular insufficiency in mice. PLoS One. 2009 Dec 21;4(12):e8380. doi: 10.1371/journal.pone.0008380.

  PMID: 20027220 BACKGROUND

• Tabibiazar R, Cheung L, Han J, Swanson J, Beilhack A, An A, Dadras SS, Rockson N, Joshi S, Wagner R, Rockson SG. Inflammatory manifestations of experimental lymphatic insufficiency. PLoS Med. 2006 Jul;3(7):e254. doi: 10.1371/journal.pmed.0030254.

  PMID: 16834456 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples

MeSH Terms

Conditions

Lymphedema

Interventions

Ketoprofen

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Stanley G Rockson

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Allan and Tina Neill Professor of Lymphatic Research and Medicine

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: December 21, 2018
• Study Start: June 21, 2019
• Primary Completion: March 31, 2023
• Study Completion: August 31, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will become available 12 months after completion of the last enrollment in the trial.
• Access Criteria: Data access requests will be reviewed by PI and Stanford IRB. If approved, requestors will be required to sign a data use agreement (DUA).

Locations

US (1)