Actinic KeratosesPhase 4NCT01935531
Effects of Topical Diclofenac on Tumor Metabolism
A Phase 4 study testing 3% diclofenac in 2.5% hyaluronic acid gel in people with Actinic Keratoses, run by University Hospital Regensburg at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Actinic Keratoses
- What is being tested?
- 3% diclofenac in 2.5% hyaluronic acid gel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteGermany
- Study dates
- Jun 2013to Mar 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Actinic Keratoses
- Being tested
- 3% diclofenac in 2.5% hyaluronic acid gel
- Keywords
- actinic keratoses, tumor metabolism, glycolysis, diclofenac, warburg effect
- Medical subject headings
- Keratosis, Actinic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3% diclofenac in 2.5% hyaluronic acid gelDrug
Also called Solaraze Gel
| Study group | Role | What they receive |
|---|---|---|
| Diclofenac | Experimental | 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. Receives: Drug: 3% diclofenac in 2.5% hyaluronic acid gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lactate level in skin biopsies of actinic keratoses
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.
Measured: 4 weeks after the treatment
Secondary outcomes (3)
Lactate level in skin biopsies of healthy skin in a subpopulation
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
Measured: Before treatment and 4 weeks after the treatment
Glycolysis-relevant proteins evaluated using PCR and Westernblot techniques
Glycolysis-relevant proteins evaluated using PCR and Westernblot techniques
Measured: at the end of the treatment and 4 weeks after the treatment
Metabolic changes (e.g. glucose, amino acids)
Metabolic changes (e.g. glucose, amino acids) evaluated by NMR methods and bioluminescence imaging techniques
Measured: at the end of the tretment and 4 weeks after the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2013 (estimated)
- Study startJun 2013
- Primary completionJan 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Actinic KeratosesStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Regensburg
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation
- Responsible party
- Principal investigator, Professor Dr. Sigrid Karrer, University Hospital Regensburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01935531
- Sponsor's protocol ID
- Diclo-TuMet_01
- Status last verified
- Mar 2016
- First submitted
- 30 Aug 2013
- Last updated
- 31 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Singer K, Dettmer K, Unger P, Schonhammer 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.
PubMed 31334125
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01935531
- Acronym / sponsor ID
- Diclo-TuMet_01
- Conditions
- Actinic Keratoses
- Keywords
- actinic keratoses, tumor metabolism, glycolysis, diclofenac, warburg effect
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University Hospital RegensburgUniversity, hospital or other
- Collaborators
- German Research Foundation
- Study start
- Jun 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 5 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Diclofenac | Experimental | Drug: 3% diclofenac in 2.5% hyaluronic acid gel3 % 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (23 listed)
- 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
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 |
|---|---|---|
| 3% diclofenac in 2.5% hyaluronic acid gelAlso: Solaraze Gel | Drug | Diclofenac |
Primary outcome
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.
3 secondary outcomes
Lactate level in skin biopsies of healthy skin in a subpopulation
Time frame: Before treatment and 4 weeks after the treatment
Glycolysis-relevant proteins evaluated using PCR and Westernblot techniques
Time frame: at the end of the treatment and 4 weeks after the treatment
Metabolic changes (e.g. glucose, amino acids)
Time frame: at the end of the tretment and 4 weeks after the treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2016.
- Derived from this study: PubMed 31334125Singer K, Dettmer K, Unger P, Schonhammer 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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 3% diclofenac in 2.5% hyaluronic acid gel in people with Actinic Keratoses, run by University Hospital Regensburg at 1 site in Germany.
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 6 inclusion and 23 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 31 Mar 2016. 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 Germany. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Lactate level in skin biopsies of actinic keratoses (time frame: 4 weeks after the treatment). 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 NCT01935531, 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 31 Mar 2016.