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Effects of Topical Diclofenac on Tumor Metabolism

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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

Study Description
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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.


Condition or disease Intervention/treatment Phase
Actinic Keratoses Drug: 3% diclofenac in 2.5% hyaluronic acid gel Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: 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
Study Start Date : June 2013
Actual Primary Completion Date : January 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy

Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: 3% diclofenac in 2.5% hyaluronic acid gel
Other Name: Solaraze Gel


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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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): NCT01935531


Locations
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Germany
University hospital Regensburg
Regensburg, Bavaria, Germany, 93053
Sponsors and Collaborators
University Hospital Regensburg
German Research Foundation
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Professor Dr. Sigrid Karrer, Professor Dr., University Hospital Regensburg
ClinicalTrials.gov Identifier: NCT01935531    
Other Study ID Numbers: Diclo-TuMet_01
First Posted: September 5, 2013    Key Record Dates
Last Update Posted: March 31, 2016
Last Verified: March 2016
Keywords provided by Professor Dr. Sigrid Karrer, University Hospital Regensburg:
actinic keratoses
tumor metabolism
glycolysis
diclofenac
warburg effect
Additional relevant MeSH terms:
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Keratosis, Actinic
Keratosis
Skin Diseases
Precancerous Conditions
Neoplasms
Diclofenac
Hyaluronic Acid
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
Adjuvants, Immunologic
Immunologic Factors
Viscosupplements
Protective Agents