Effects of Topical Diclofenac on Tumor Metabolism

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University Hospital Regensburg
Sponsor:
Collaborator:
German Research Foundation
Information provided by (Responsible Party):
Professor Dr. Sigrid Karrer, University Hospital Regensburg
ClinicalTrials.gov Identifier:
NCT01935531
First received: August 30, 2013
Last updated: September 4, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Actinic Keratoses
Drug: 3% diclofenac in 2.5% hyaluronic acid gel
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Hospital Regensburg:

Primary Outcome Measures:
  • Lactate level in skin biopsies of actinic keratoses [ Time Frame: 4 weeks after the treatment ] [ Designated as safety issue: No ]
    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:
  • Lactate level in skin biopsies of healthy skin in a subpopulation [ Time Frame: Before treatment and 4 weeks after the treatment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Metabolic changes (e.g. glucose, amino acids) evaluated by NMR methods and bioluminescence imaging techniques


Estimated Enrollment: 38
Study Start Date: June 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 3% diclofenac in 2.5% hyaluronic acid gel
    Other Name: Solaraze Gel
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01935531

Contacts
Contact: Sigrid Karrer, Professor 00499419449656 sigrid.karrer@klinik.ukr.de

Locations
Germany
University hospital Regensburg Recruiting
Regensburg, Bavaria, Germany, 93053
Contact: Sigrid Karrer, Professor    00499419449656    sigrid.karrer@klinik.ukr.de   
Sub-Investigator: Elisabeth A. Kohl, MD         
Sponsors and Collaborators
University Hospital Regensburg
German Research Foundation
  More Information

No publications provided

Responsible Party: Professor Dr. Sigrid Karrer, Professor Dr., University Hospital Regensburg
ClinicalTrials.gov Identifier: NCT01935531     History of Changes
Other Study ID Numbers: Diclo-TuMet_01
Study First Received: August 30, 2013
Last Updated: September 4, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Regensburg:
actinic keratoses
tumor metabolism
glycolysis
diclofenac
warburg effect

Additional relevant MeSH terms:
Keratosis
Keratosis, Actinic
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
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Adjuvants, Immunologic
Immunologic Factors
Viscosupplements
Protective Agents

ClinicalTrials.gov processed this record on August 28, 2014