Diclofenac for Alcohol Use Disorder

(DKMOI Trial)

Overseen By AnneMarie Kearns, BS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Maryland, Baltimore

Must not be taking: NSAIDs, Anticoagulants, Corticosteroids, others

Disqualifiers: Schizophrenia, Bipolar, Opioid use, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day per session

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This mechanistic, proof of concept laboratory study will test the pharmacological properties of diclofenac in individuals with AUD. Participants will complete two sessions in which they will receive a single dose of diclofenac (100 mg) or matched placebo in a randomized and double blind fashion. The primary aim is to assess whether this dose of diclofenac, vs. placebo, increases circulating levels of kynurenic acid. This finding would provide evidence that diclofenac (100 mg) inhibits the kynurenine 3-monooxygenase enzyme.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications if they contraindicate the use of diclofenac, such as oral corticosteroids, anticoagulants, lithium, warfarin, aspirin, methotrexate, cyclosporine, ACE-inhibitors, and some diuretics. The protocol does not specify a washout period, but you should discuss your current medications with the study team to determine if any changes are needed.

Is diclofenac generally safe for humans?

Diclofenac has been used worldwide since 1974 and is generally considered safe, with studies showing it is better tolerated than aspirin and comparable to ibuprofen and naproxen. It has been safely used in both short-term and long-term trials, with adverse effects being infrequent and usually mild. ^{1 2 3 4 5}

What makes the drug Diclofenac unique for treating Alcohol Use Disorder?

Diclofenac is traditionally used as a pain reliever and anti-inflammatory medication, making its use for Alcohol Use Disorder novel, as it may work differently from standard treatments like counseling or medications targeting brain chemistry. ^{6 7 8 9 10}

Research Team

Daniel Roche, PhD

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

This trial is for individuals aged 21-65 with Alcohol Use Disorder (AUD) of any severity, who are not pregnant or nursing, and do not use certain drugs. Participants must not be on medications that interact with diclofenac, seeking AUD treatment, or have had recent substance abuse other than alcohol and nicotine.

Inclusion Criteria

You have been diagnosed with Alcohol Use Disorder (AUD) according to the DSM-5 guidelines, regardless of its severity (mild, moderate, or severe).

I am between 21 and 65 years old.

Exclusion Criteria

You have had allergic reactions to medications like NSAIDs (non-steroidal anti-inflammatory drugs) and aspirin in the past.

AST and ALT > four times the upper limit of the normal range, or albumin, GFR, BUN, or creatinine 15% > the upper limit of the normal range

I do not have any autoimmune, inflammatory disorders, or conditions like uncontrolled heart disease, kidney disease, liver disease, high blood pressure, or diabetes that could affect my safety in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of diclofenac (100 mg) or placebo in two sessions

1 day per session

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Diclofenac

Trial Overview The study tests if a single dose of diclofenac (100 mg) can increase kynurenic acid levels in the blood compared to a placebo. This could show whether diclofenac inhibits an enzyme related to AUD. The process is randomized and double-blind.

Participant Groups

Group I: Diclofenac Active Control 1 Intervention

Participants will take a single 100mg dose of diclofenac.

Group II: Placebo Placebo Group 1 Intervention

Participants will take a single dose of placebo.

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?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

Data from over 100,000 patients indicate that diclofenac is safe and well-tolerated, with adverse effects being infrequent and generally mild, especially when compared to placebo and other NSAIDs.

Long-term use of diclofenac (over a year) has shown no significant increase in adverse effects for older patients compared to younger patients, making it a reliable option for treating various rheumatic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Worldwide clinical safety experience with diclofenac. Willkens, RF.[2019]

Diclofenac has been shown to be effective in treating conditions like rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis, based on extensive clinical studies worldwide.

Its safety and efficacy are comparable to other NSAIDs, with the added benefit of a short serum half-life and long-lasting effects in synovial fluid, allowing for convenient twice-daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclofenac. Ogle, C.[2013]

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]

In a double-blind trial involving hospitalized patients with rheumatoid arthritis, both diclofenac sodium (50 mg b.i.d.) and naproxen (250 mg b.i.d.) effectively reduced morning stiffness, improved grip strength, and alleviated pain, showing no significant difference in clinical efficacy between the two.

Diclofenac sodium was associated with fewer unwanted side effects compared to naproxen, with only three patients on diclofenac reporting adverse effects versus seven on naproxen, suggesting it may be a better-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclofenac sodium (Voltaren) and naproxen in the treatment of rheumatoid arthritis: a comparative double-blind study. Kajander, A., Martio, J.[2019]

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]

Etanercept, the first biological disease-modifying antirheumatic drug approved over 15 years ago, effectively reduces symptoms and improves quality of life in patients with various rheumatic diseases, including rheumatoid arthritis and psoriatic arthritis, with benefits sustained during long-term treatment.

The safety profile of etanercept is consistent with its approved labeling, showing manageable adverse events, making it a cost-effective and central treatment option for autoimmune rheumatic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept: a review of its use in autoimmune inflammatory diseases. Scott, LJ.[2022]

A total of 344 patients in the UK reported their baseline characteristics and health-related quality of life before starting etanercept, a treatment for various chronic conditions, with a mean age of 53 years and predominantly female participants (62%).

The study highlighted that 56% of patients were treated for rheumatoid arthritis, and notably, 38% of those with rheumatoid arthritis were not on methotrexate, indicating a potential area for further investigation regarding treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline characteristics and patient reported outcome data of patients prescribed etanercept: web-based and telephone evaluation. Wade, AG., Crawford, GM., Pumford, N., et al.[2021]

Etanercept is an effective treatment for various autoimmune conditions, including rheumatoid arthritis and psoriasis, and is being explored for additional off-label uses, indicating its versatility as a therapeutic option.

While etanercept has rare side effects, both cutaneous and systemic, the overall safety profile suggests it is a promising medication with substantial benefits, likely leading to increased usage in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The medical uses and side effects of etanercept with a focus on cutaneous disease. Scheinfeld, N.[2015]

In a study involving 77 patients with rheumatoid arthritis or psoriatic arthritis, the AutoTouch™ autoinjector achieved a high success rate of 97.8% for self-injections over 5 weeks, indicating its efficacy for patient use.

In a preference study with 216 patients, 41.7% preferred AutoTouch™ over the SureClick® autoinjector, citing advantages in ease of use and injection monitoring, although SureClick® was favored for fewer steps and less discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel electromechanical autoinjector, AutoTouch™, for self-injection of etanercept: real-world use and benefits. Collier, DH., Bitman, B., Coles, A., et al.[2022]

Lisinopril oral solution (Qbrelis) is effective for treating hypertension, heart failure, and acute myocardial infarction, providing a liquid alternative for patients who may have difficulty swallowing pills.

Etanercept-szzs (Erelzi) is used for multiple autoimmune disorders, offering a biosimilar option to patients, while lumacaftor/ivacaftor (Orkambi) is specifically designed to improve lung function in cystic fibrosis patients by targeting the underlying genetic defect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Kaufman, MB.[2020]

References

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

Worldwide clinical safety experience with diclofenac. [2019]

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

Diclofenac. [2013]

3. Croatia pubmed.ncbi.nlm.nih.gov

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

4. Norway pubmed.ncbi.nlm.nih.gov

Diclofenac sodium (Voltaren) and naproxen in the treatment of rheumatoid arthritis: a comparative double-blind study. [2019]

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

Worldwide safety experience with diclofenac. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Etanercept: a review of its use in autoimmune inflammatory diseases. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Baseline characteristics and patient reported outcome data of patients prescribed etanercept: web-based and telephone evaluation. [2021]

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

The medical uses and side effects of etanercept with a focus on cutaneous disease. [2015]

9. England pubmed.ncbi.nlm.nih.gov

A novel electromechanical autoinjector, AutoTouch™, for self-injection of etanercept: real-world use and benefits. [2022]

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

Pharmaceutical Approval Update. [2020]