Diclofenac + Curcumin for Drug Interactions

Overseen By Siavosh Naji-Talakar, PharmD, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington State University

Must not be taking: Turmeric, Curcumin, others

Disqualifiers: Tobacco, Cannabis, Major illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this pilot study is to gather preliminary data on the (1) contribution of the understudied drug metabolizing enzyme, UDP-glucuronosyltransferase (UGT) 2B17, to the metabolism of a widely used medication, diclofenac, and (2) impact of the UGT2B17 inhibitor and natural product, curcumin, on diclofenac pharmacokinetics. Results will inform future studies aimed to assess the effects of UGT2B17 genetic polymorphisms and co-consumed xenobiotics on the pharmacokinetics and toxicity risk of diclofenac and other UGT2B17 drug substrates.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications or supplements that are known to affect how diclofenac or curcumin work in your body.

What evidence supports the effectiveness of the drug combination of diclofenac and curcumin?

Research suggests that combining diclofenac and curcumin can have a synergistic effect, meaning they work better together to reduce pain and inflammation than when used separately. This combination was shown to be effective in reducing pain in animal studies, indicating potential benefits for treating inflammatory pain in humans. ^{1 2 3 4 5}

Is diclofenac generally safe for human use?

Diclofenac has been used worldwide since 1974, and safety data show it is generally well-tolerated and safer than aspirin, with a safety profile comparable to ibuprofen and naproxen. It has been studied for effects on various body systems and is considered safe for use in children and the elderly, with attention to potential drug interactions. ^{6 7 8 9 10}

What makes the diclofenac and curcumin drug combination unique?

The combination of diclofenac and curcumin is unique because it uses a synergistic effect to enhance pain relief and reduce inflammation, allowing for lower doses and minimizing side effects compared to using diclofenac alone. ^{2 5 11 12 13}

Eligibility Criteria

This trial is for healthy adults aged 18-64 who don't have major illnesses like kidney or liver disease, diabetes, heart conditions, or cancer. Participants must not be on medications that affect diclofenac or curcumin and should avoid caffeine and alcohol before study days. They can't smoke, use cannabis products, be pregnant/nursing, or planning pregnancy soon after the trial.

Inclusion Criteria

I am not on medications or supplements that affect diclofenac or curcumin.

I have signed the consent form and can follow the study's requirements.

I agree to use non-hormonal birth control methods.

Exclusion Criteria

You have a history of addiction to drugs or alcohol, or a serious mental illness.

I have a major or chronic illness like kidney disease or diabetes.

I have a history of anemia or other significant blood disorders.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

A single dose of diclofenac (25 mg capsule) is administered to participants genotyped as extensive and poor metabolizers. Plasma and urine are collected from 0-12 hours.

1 day

1 visit (in-person)

Washout

A washout period of at least 3 days between Treatment Phase 1 and Treatment Phase 2.

3 days

Treatment Phase 2

A single oral dose of diclofenac (25 mg capsule) and curcumin (2,000 mg tablet) is administered to participants genotyped as extensive metabolizers. Plasma and urine are collected from 0-12 hours.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

Treatment Details

Interventions

• Curcumin
• Diclofenac

Trial Overview The study is testing how a natural product called curcumin affects the breakdown of diclofenac—a common pain reliever—by inhibiting an enzyme known as UGT2B17. This pilot study will help design future research on genetic differences in drug metabolism and potential toxicity risks.

Participant Groups

Group I: Arm 2: diclofenac + curcumin Experimental Treatment 2 Interventions

A single oral dose of diclofenac (25 mg capsule) and a single oral dose of curcumin (2,000 mg tablet) will be administered by mouth to the 5 participants genotyped as extensive metabolizers. Plasma and urine will be collected from 0-12 hours.

Group II: Arm 1: diclofenac alone (baseline) Experimental Treatment 1 Intervention

A single dose of diclofenac (25 mg capsule) will be administered by mouth to 5 participants (minimum 2 females) genotyped as extensive metabolizers (Arm 1A) and 5 participants (minimum 2 females) genotyped as poor metabolizers (Arm 1B). Plasma and urine will be collected from 0-12 hours. A washout of at least 3 days will elapse between Arm 1 and Arm 2.

Diclofenac is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Voltaren for:

• Ankylosing Spondylitis
• Aseptic Necrosis
• Back Pain
• Chronic Pain
• Frozen Shoulder
• Headache
• Migraine
• Muscle Pain
• Osteoarthritis
• Pain
• Period Pain
• Rheumatoid Arthritis
• Sciatica
• Spondyloarthritis

Approved in European Union as Voltaren for:

• Osteoarthritis
• Rheumatoid Arthritis
• Ankylosing Spondylitis
• Migraine
• Pain
• Dysmenorrhea

Approved in Canada as Voltaren for:

• Osteoarthritis
• Rheumatoid Arthritis
• Ankylosing Spondylitis
• Migraine
• Pain
• Dysmenorrhea

Who Is Running the Clinical Trial?

Washington State University

Lead Sponsor

Trials

114

Recruited

58,800+

Findings from Research

In a trial involving 30 patients with osteo-arthrosis, diclofenac (Voltaren) provided greater relief from pain and stiffness compared to naproxen over a two-week period.

Voltaren was better tolerated than naproxen, with fewer patients reporting side effects and those who did experienced less severe complaints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclofenac (Voltaren) for the treatment of osteo-arthrosis: a double-blind comparison with naproxen. Siraux, P.[2017]

The combination of curcumin and diclofenac in rats showed a synergistic effect in reducing pain, allowing for lower doses of diclofenac to achieve the same antinociceptive effect, which could help minimize side effects.

The study found that curcumin did not significantly affect the bioavailability of diclofenac, indicating that the enhanced pain relief from the combination is likely due to a direct interaction at the systemic level rather than changes in how the body absorbs the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats. De Paz-Campos, MA., Ortiz, MI., Chávez Piña, AE., et al.[2014]

In a double-blind study involving 120 patients with soft-tissue rheumatism, both diclofenac sodium and naproxen were found to be effective in relieving symptoms, with similar overall therapeutic efficacy.

Diclofenac sodium showed significantly better results in treating shoulder-related conditions compared to naproxen, and both medications had a low incidence of unwanted side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative short-term trial with Voltaren (diclofenac sodium) and naproxen in soft-tissue rheumatism. Valtonen, EJ.[2019]

Diclofenac (VOLTAREN) is effective for various conditions treated with NSAIDs, showing good tolerability and a favorable balance between COX-2 and COX-1 inhibition, which may reduce side effects.

The drug is available in multiple forms and has a long history of use, but caution is advised for patients at risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Voltaren--the gold standard]. Babić-Naglić, D.[2013]

The study developed a controlled release gel formulation combining curcumin microspheres and diclofenac diethylamine, which showed improved anti-inflammatory effects compared to a marketed gel, reducing inflammation by 72.53% versus 50.75%.

In vitro diffusion studies indicated that the new gel formulation provided a more controlled release of the active ingredients, achieving 92.16% diffusion in 3 hours, compared to 79.57% for the marketed gel, suggesting enhanced delivery and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled Release Gel Encompassing Curcumin Microspheres and Diclofenac Diethylamine for Feat Against Arthritis Inflammation. Singh, P., Dabre, S.[2021]

Diclofenac sodium has been used worldwide since 1974, and extensive safety data indicate it is safer and better tolerated than aspirin, with safety comparable to ibuprofen and naproxen.

Clinical trials in the U.S. show that patients taking diclofenac (150 mg daily) experienced fewer adverse reactions compared to those on other nonsteroidal anti-inflammatory drugs, except for naproxen at 500 mg daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Worldwide safety experience with diclofenac. Catalano, MA.[2019]

Drug-drug interactions (DDIs) are a growing concern in modern medicine, especially as more patients with multiple health conditions (polypharmacy) take several medications, leading to an exponential increase in potential DDIs.

The article reviews both pharmacodynamic and pharmacokinetic DDIs, highlighting the importance of understanding these interactions to prevent unwanted side effects and improve patient safety, particularly in an aging population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug-drug interactions you should know!] Voigt, N., Ort, K., Sossalla, S.[2019]

Drug-drug interactions (DDIs) are a growing concern in modern medicine, especially as more patients with multiple health conditions (polypharmacy) take several medications, leading to an exponential increase in potential DDIs.

The article reviews both pharmacodynamic and pharmacokinetic DDIs, particularly those involving the cytochrome P450 system, and offers tools for clinicians to identify and prevent these interactions, which could ultimately reduce patient mortality and morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug-drug interactions you should know!] Voigt, N., Ort, K., Sossalla, S.[2019]

Drug-drug interactions (DDIs) are a growing concern in modern medicine, especially as more patients with multiple health conditions (polypharmacy) take several medications, leading to an exponential increase in potential DDIs.

The article reviews both pharmacodynamic and pharmacokinetic DDIs, particularly those involving the cytochrome P450 system, and offers tools for clinicians to identify and prevent these interactions, which could ultimately reduce patient mortality and morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug-drug Interactions You Should Know!] Voigt, N., Ort, K., Sossalla, S.[2019]

Out of 2,195 serious adverse drug reaction (ADR) reports analyzed, 381 (17.4%) were linked to actual drug-drug interactions (DDIs), indicating that about one-third of patients with potential DDIs experienced serious ADRs.

Warfarin was frequently involved in these interactions, with the most common serious ADRs being gastrointestinal or cerebral hemorrhagic events, particularly with combinations like proton pump inhibitors/warfarin and platelet aggregation inhibitors/warfarin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database. Magro, L., Arzenton, E., Leone, R., et al.[2021]

Diclofenac sodium, the active ingredient in Voltaren, has been shown to effectively reduce inflammation and pain in animal models, demonstrating its analgesic and anti-inflammatory properties.

The compound has a favorable safety profile compared to other nonsteroidal anti-inflammatory drugs, as indicated by its tolerability metrics, and it works by inhibiting cyclo-oxygenase and lipoxygenase pathways, which are crucial in the inflammatory response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of diclofenac sodium. Scholer, DW., Ku, EC., Boettcher, I., et al.[2019]

Chronic exposure to diclofenac sodium in male rabbits for 70 days resulted in significant ultrastructural changes in renal tissues, including mitochondrial swelling and endoplasmic reticulum dilation.

These alterations suggest potential renal toxicity from long-term use of diclofenac sodium, highlighting the need for careful monitoring of kidney health in patients using this common NSAID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrastructural alterations in renal tissues of rabbits induced by diclofenac sodium (Voltaren). Taib, NT., Jarrar, BM., Mubarak, MM.[2013]

In a double-blind trial involving 60 arthritic patients over 12 weeks, diclofenac sodium (Voltaren) and indometacin showed no significant differences in overall effectiveness or tolerance for treating osteoarthritic symptoms.

However, patients taking Voltaren experienced an earlier onset of relief from symptoms compared to those taking indometacin, suggesting a potential advantage in the speed of action for Voltaren.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of arthrosis with a new non-steroid anti-rheumatic agent (Voltaren). A double blind comparison with indomethacin]. Wagenhäuser, FJ., Narozna, H.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Diclofenac (Voltaren) for the treatment of osteo-arthrosis: a double-blind comparison with naproxen. [2017]

2. Germany pubmed.ncbi.nlm.nih.gov

Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats. [2014]

3. Norway pubmed.ncbi.nlm.nih.gov

A comparative short-term trial with Voltaren (diclofenac sodium) and naproxen in soft-tissue rheumatism. [2019]

4. Croatia pubmed.ncbi.nlm.nih.gov

[Voltaren--the gold standard]. [2013]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Controlled Release Gel Encompassing Curcumin Microspheres and Diclofenac Diethylamine for Feat Against Arthritis Inflammation. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Worldwide safety experience with diclofenac. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

[Drug-drug interactions you should know!] [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

[Drug-drug interactions you should know!] [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

[Drug-drug Interactions You Should Know!] [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Pharmacology of diclofenac sodium. [2019]

12. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Ultrastructural alterations in renal tissues of rabbits induced by diclofenac sodium (Voltaren). [2013]

13. Switzerland pubmed.ncbi.nlm.nih.gov

[Treatment of arthrosis with a new non-steroid anti-rheumatic agent (Voltaren). A double blind comparison with indomethacin]. [2013]