Diclofenac for Alcohol Use Disorder

Overseen By Mathew Glassman, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Maryland, Baltimore

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

Disqualifiers: Schizophrenia, Bipolar, Cardiovascular, others

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

Compensation: Varies

Number of Visits: 4

Duration: 5 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests diclofenac, a common pain reliever, to determine if it can help treat alcohol use disorder (AUD) by affecting certain brain chemicals. The goal is to discover whether diclofenac can safely increase a protective brain chemical (KYNA) and decrease a harmful one (QUIN), potentially reducing alcohol cravings and negative moods. Participants will receive different doses or a placebo (a pill with no active drug) to identify the most effective option. Individuals who drink heavily, have not recently undergone treatment, and are not on certain medications might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that contraindicate the use of diclofenac, such as oral corticosteroids, anticoagulants, lithium, warfarin, aspirin (daily use), methotrexate, cyclosporine, ACE-inhibitors, and certain diuretics. If you are on any of these medications, you may need to stop them to participate in the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that diclofenac, a medication approved by the FDA for other uses, is generally safe for use. It has treated pain and swelling for years. However, diclofenac carries a known risk of stomach bleeding, particularly when combined with alcohol. This is crucial because the current study focuses on individuals with Alcohol Use Disorder (AUD).

Past experiences with diclofenac indicate the importance of monitoring liver health. Doctors typically check liver enzymes in the first few weeks of treatment to ensure proper liver function. This process involves verifying that the liver is functioning well.

In summary, diclofenac has a history of safe use at approved doses, but awareness of risks like stomach bleeding is essential, especially with alcohol consumption. This study aims to understand its safety in individuals with AUD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcohol use disorder?

Researchers are excited about using Diclofenac for Alcohol Use Disorder because it offers a novel approach compared to traditional treatments like naltrexone, acamprosate, or disulfiram, which mainly target neurotransmitter systems. Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), is being explored for its potential to reduce inflammation and alter immune responses, which are thought to play a role in addiction and alcohol cravings. This unique mechanism could offer an alternative pathway for managing alcohol use disorder, potentially benefiting those who do not respond to current treatments. Additionally, Diclofenac's established safety profile for other conditions may streamline its development for this new use.

What evidence suggests that diclofenac might be an effective treatment for alcohol use disorder?

Research has shown that diclofenac, a common pain reliever, might help treat alcohol use disorder (AUD) by affecting a specific brain pathway. This pathway produces substances that can either protect or harm brain cells. In animal studies, diclofenac increased the production of protective substances, resulting in reduced alcohol use and fewer cravings. Although diclofenac has demonstrated these effects in animals, its effectiveness in humans with AUD remains uncertain. This trial will test different dosages of diclofenac to determine if it can induce these protective changes in people. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals with Alcohol Use Disorder (AUD). Participants will undergo four sessions where they'll receive different doses of Diclofenac or a placebo to see if it affects their craving and mood.

Inclusion Criteria

Meet DSM-5 diagnostic criteria for current AUD of any severity (Mild, Moderate, or Severe)

In the 30-day period before enrollment, engage in heavy drinking (5 or more drinks for men, 4 or more drinks for women) 5 times per month or more

I am between 21 and 65 years old.

Exclusion Criteria

Current (last 12 months) DSM-5 diagnosis of SUD for any psychoactive substances other than alcohol, nicotine, and cannabis (cannabis use disorder, mild severity allowed; moderate and severe excluded)

Lifetime DSM-5 diagnosis of schizophrenia spectrum and other psychotic disorders and bipolar and related disorders

Positive urine toxicology screen for cocaine, opiates, amphetamines, methamphetamine, phencyclidine, barbiturates, benzodiazepine, methadone, and tricyclic antidepressants

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive diclofenac (50, 75, or 100 mg) or placebo across four sessions to assess changes in KYNA and QUIN levels, alcohol craving, and negative mood.

5 weeks

4 sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diclofenac

Trial Overview The study tests whether Diclofenac, at doses of 50mg, 75mg, or 100mg, can increase KYNA levels in the brain and reduce alcohol-related behaviors compared to a placebo in people with AUD.

How Is the Trial Designed?

Group I: Diclofenac 50mg Active Control 1 Intervention

In this arm participants will receive 50mg of Diclofenac

Group II: Diclofenac 75mg Active Control 1 Intervention

In this arm participants will receive 75mg of Diclofenac

Group III: Diclofenac 100mg Active Control 1 Intervention

In this arm participants will receive 100mg of Diclofenac

Group IV: Placebo Placebo Group 1 Intervention

Placebo arm

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+

Published Research Related to This Trial

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]

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]

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]

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, 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]

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]

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]

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 (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]

Citations

1. withpower.com withpower.com/trial/early-phase-1-alcoholism-10-2023-2da2d

Diclofenac for Alcohol Use Disorder (DKMOI Trial) This mechanistic, proof of concept laboratory study will test the pharmacological properties of diclofenac in individuals with AUD.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06636227?term=KMO&viewType=Table&rank=1

NCT06636227 | Diclofenac Dose Response Study Investigators propose to conduct a human laboratory pilot study to test whether diclofenac can increase KYNA in individuals with AUD, and if so, which of 3 ...

3. trialx.com trialx.com/clinical-trials/listings/323976/diclofenac-dose-response-study/

Diclofenac Dose Response Study Individuals with AUD (n = 24) will complete four sessions where they receive diclofenac (50, 75, or 100 mg) or placebo. Investigators will ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6328471/

The Use of Baclofen as a Treatment for Alcohol Use Disorder A recent meta-analysis found better results among studies using lower doses of baclofen compared to studies using higher doses [(69); see Table 2]. The use ...

5. withpower.com withpower.com/trial/phase-1-alcohol-related-disorders-11-2024-3ce9f

Diclofenac for Alcohol Use Disorder Trial Overview The study tests whether Diclofenac, at doses of 50mg, 75mg, or 100mg, can increase KYNA levels in the brain and reduce alcohol-related behaviors ...

6. drugs.com drugs.com/food-interactions/diclofenac,cataflam.html

Cataflam and Alcohol/Food Interactions Do not drink alcohol while taking diclofenac. Alcohol can increase your risk of stomach bleeding caused by diclofenac.

7. mayoclinic.org mayoclinic.org/drugs-supplements/diclofenac-oral-route/description/drg-20069748

Diclofenac (oral route) - Side effects & dosage Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your ...

8. webmd.com webmd.com/drugs/2/drug-4284-4049/diclofenac-oral/diclofenac-sodium-enteric-coated-tablet-oral/details

Diclofenac (Cataflam, Voltaren, others) - Uses, Side Effects, ... It is unknown if drinking alcohol will affect diclofenac, but both diclofenac and alcohol can increase your risk of bleeding. It is best to ...

9. niaaa.nih.gov niaaa.nih.gov/publications/brochures-and-fact-sheets/harmful-interactions-mixing-alcohol-with-medicines

Harmful Interactions | National Institute on Alcohol Abuse and ... Mixing alcohol with certain medications can cause nausea and vomiting, headaches, drowsiness, fainting, or loss of coordination.

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/020142s029lbl.pdf

CATAFLAM® - accessdata.fda.gov Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac. ...