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Effects of Topical Diclofenac on Tumor Metabolism

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: NCT01935531
Recruitment Status : Completed
First Posted : September 5, 2013
Last Update Posted : March 31, 2016
Sponsor:
Collaborator:
German Research Foundation
Information provided by (Responsible Party):
Professor Dr. Sigrid Karrer, University Hospital Regensburg

Tracking Information
First Submitted Date  ICMJE August 30, 2013
First Posted Date  ICMJE September 5, 2013
Last Update Posted Date March 31, 2016
Study Start Date  ICMJE June 2013
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2013)
Lactate level in skin biopsies of actinic keratoses [ Time Frame: 4 weeks after the treatment ]
Assessment of the effects of topical 3% diclofenac in 2.5% hyaluronic acid gel on lactate level in skin biopsies of actinic keratoses. Skin biopsies of actinic keratoses are obtained prior to treatment and 4 weeks after the treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2013)
  • Lactate level in skin biopsies of healthy skin in a subpopulation [ Time Frame: Before treatment and 4 weeks after the treatment ]
    Assessment of the effects of topical 3% diclofenac in 2.5% hyaluronic acid gel on lactate level in skin biopsies of actinic keratoses compared to untreated sun damaged, healthy skin in a subpopulation
  • Glycolysis-relevant proteins evaluated using PCR and Westernblot techniques [ Time Frame: at the end of the treatment and 4 weeks after the treatment ]
    Glycolysis-relevant proteins evaluated using PCR and Westernblot techniques
  • Metabolic changes (e.g. glucose, amino acids) [ Time Frame: at the end of the tretment and 4 weeks after the treatment ]
    Metabolic changes (e.g. glucose, amino acids) evaluated by NMR methods and bioluminescence imaging techniques
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Topical Diclofenac on Tumor Metabolism
Official Title  ICMJE Prospective, Controlled and Monocentric Study to Evaluate the Effects of Topical 3% Diclofenac in 2.5% Hyaluronic Acid Gel on Tumor Metabolism in the Treatment of Actinic Keratoses in Immunocompetent and Immunocompromised Patients
Brief Summary

The rationale of this study is to investigate the effects of topical diclofenac on tumor metabolism in the treatment of actinic keratoses in immunocompetent and immunocompromised patients.

Study hypothesis is that topical diclofenac lowers lactate level in skin biopsies of actinic keratoses. Planned number of patients is 38.

This study is a monocenter study investigating the effects of 3% diclofenac in 2.5% hyaluronic acid gel on tumor metabolism in the treatment of actinic keratoses. Treatment duration is 3 months. Skin biopsies will be obtained before treatment, at the end of the treatment and four weeks after the treatment. Control biopsies at visit 1 and 3 are performed in healthy, sun damaged and untreated skin. Evaluation of efficacy will be performed at the end of the treatment and four weeks after the treatment.

Duration of treatment is 3 months (±4 weeks). Approximately 0,5g Solaraze® 3% gel is applied on a 5cm x 5cm lesion. Solaraze® 3% gel is applied twice daily on the study lesions.

Detailed Description Neoplastic cells show an increased glucose metabolism and glycolysis which is associated with high lactate concentrations. There is also data for several tumor entities that high levels of lactate in the tumor are associated with tumor progression, metastasis and poor clinical outcome. Kreutz et al. demonstrated that diclofenac inhibits tumor cell proliferation in vitro and tumor growth in vivo via COX-independent effects on glucose metabolism. Diclofenac is taken up by tumor cells and inhibits tumor cell proliferation through inhibition of the oncogene MYC and subsequently glycolysis and block of lactate transport. MYC regulates genes involved in glycolysis and is upregulated in neoplastic cells, which is in line with the metabolic switch to glycolysis, the so called "Warburg effect", that cancer cells show. Although these results were found in vitro using human melanoma cells and in vivo in a mouse model, a similar mechanism of action is assumed to be relevant for the treatment of actinic keratoses with topical diclofenac. However tumor metabolism in diclofenac-treated actinic keratoses has never been investigated. To investigate the mechanism of action of diclofenac in the treatment of actinic keratoses, a clinical study analyzing particularly lactate levels, glycolysis and inflammatory infiltrate is needed.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Actinic Keratoses
Intervention  ICMJE Drug: 3% diclofenac in 2.5% hyaluronic acid gel
Other Name: Solaraze Gel
Study Arms  ICMJE Experimental: Diclofenac
3 % diclofenac in 2.5% hyaluronic acid gel (Solaraze® 3% gel) is applied twice daily in the treatment area. 3 % diclofenac in 2.5% hyaluronic acid gel (Solaraze® 3% gel) is to be applied 1cm beyond the single AK.
Intervention: Drug: 3% diclofenac in 2.5% hyaluronic acid gel
Publications * Singer K, Dettmer K, Unger P, Schönhammer G, Renner K, Peter K, Siska PJ, Berneburg M, Herr W, Oefner PJ, Karrer S, Kreutz M, Datz E. Topical Diclofenac Reprograms Metabolism and Immune Cell Infiltration in Actinic Keratosis. Front Oncol. 2019 Jul 3;9:605. doi: 10.3389/fonc.2019.00605. eCollection 2019.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 4, 2013)
38
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent has been signed prior to or at Screening Visit
  • Caucasian male and female patients
  • Age > 18 years
  • Negative pregnancy test in women of childbearing age
  • Clinical diagnosis of actinic keratosis (AK)
  • A minimum of three AK lesions

Exclusion Criteria in immunocompromised patients :

  • Concomitant UV-phototherapy
  • Pregnancy or lactation
  • Women in child-bearing age who do not use highly efficient contraceptive methods (<1% failure rate per year)
  • Skin diseases that might interfere with response evaluation of study treatment
  • Topical pretreatment of the AK study lesions with photodynamic therapy, Solaraze® 3% gel, Aldara®, 5-FU, or polyphenon E during the 8 weeks preceding study treatment
  • Radiation therapy performed in the treatment area during the 3 months preceding study therapy
  • Systemic treatment with diclofenac
  • Known intolerance to diclofenac or to any other ingredient of Solaraze® 3% gel
  • Conditions that might interfere with the ability to understand the study and thus give written informed consent
  • Simultaneous participation in another clinical study or participation in another clinical study in the 30 days directly preceding inclusion
  • Suspected lack of compliance

Exclusion criteria in immunocompetent patients:

  • Concomitant UV-phototherapy
  • Pregnancy or lactation
  • Women in child-bearing age who do not use highly efficient contraceptive methods (<1% failure rate per year)
  • Patients with clinically relevant suppression of the immune system (e.g. drug induced, infection)
  • Skin diseases that might interfere with response evaluation of study treatment
  • Topical pretreatment of the AK study lesions with photodynamic therapy, Aldara®, Solaraze® 3% gel , 5-FU, or polyphenon E during the 8 weeks preceding study treatment
  • Systemic treatment with cytostatic drugs or radiation therapy performed in the treatment area during the 3 months preceding study therapy
  • Systemic treatment with diclofenac
  • Known intolerance to diclofenac or to any other ingredient of Solaraze® 3% gel
  • Conditions that might interfere with the ability to understand the study and thus give written informed consent
  • Simultaneous participation in another clinical study or participation in another clinical study in participation in another clinical study in the 30 days directly preceding inclusion
  • Suspected lack of compliance
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01935531
Other Study ID Numbers  ICMJE Diclo-TuMet_01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Professor Dr. Sigrid Karrer, University Hospital Regensburg
Study Sponsor  ICMJE University Hospital Regensburg
Collaborators  ICMJE German Research Foundation
Investigators  ICMJE Not Provided
PRS Account University Hospital Regensburg
Verification Date March 2016

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