Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Maryland, Baltimore
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?The development of efficacious medications for AUD remains a high research priority with current emphases on identifying novel molecular targets and efficiently screening new compounds. Pharmacological modulation of the kynurenine pathway (KP) represents a promising novel target for AUD. The KP is a complex enzymatic cascade with each step producing biologically active metabolites that are critically involved in diverse physiological and pathological processes. Chronic alcohol exposure produces dysregulation of the KP, particularly as evidenced by decreased levels of the neuroprotective metabolite kynurenic acid (KYNA) and increased levels of the neurotoxic metabolite quinolinic acid (QUIN). This metabolic shift is associated with various alcohol-related pathologies in animals and humans. Thus, a medication that targets the KP to restore KYNA and attenuate QUIN levels may be an effective treatment for AUD. The enzyme kynurenine 3- monooxygenase (KMO) is a major gatekeeper of the KP and resultant KYNA levels. KMO inhibition shifts the KP towards KYNA production in brain and away from QUIN production. Critically, KMO inhibition in rodents, through its increase in brain KYNA levels, decreases alcohol self-administration, preference, cue-reactivity, and relapse behaviors. However, KMO-inhibitors have not been tested in humans because of presumed lack of availability. Diclofenac is an FDA-approved Non-Steroidal Anti-Inflammatory Drug that was recently discovered to inhibit KMO activity. Consistent with KMO inhibition, diclofenac increases KYNA levels in the brain and periphery of rodents. However, it remains unknown whether diclofenac increases KYNA levels and affects alcohol-related behaviors in humans at approved, safe dosages.
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 doses (50, 75, or 100 mg) most effectively increases KYNA. Individuals with AUD (n = 24) will complete four sessions where they receive diclofenac (50, 75, or 100 mg) or placebo. Investigators will examine increases in KYA levels and will also assess QUIN levels, alcohol craving, and negative mood.
How is the drug Diclofenac unique for treating Alcohol Use Disorder?
Diclofenac is unique for treating Alcohol Use Disorder because it is primarily known as a pain reliever and anti-inflammatory medication, commonly used for conditions like arthritis, rather than for alcohol-related issues. This novel use suggests a different mechanism of action compared to traditional treatments for Alcohol Use Disorder, which typically focus on reducing cravings or withdrawal symptoms.
678910Is diclofenac generally safe for humans?
Diclofenac has been used worldwide since 1974 and is generally considered safe, with safety data showing it is better tolerated than aspirin and comparable to ibuprofen and naproxen. Studies involving over 100,000 patients indicate that adverse effects are infrequent and usually mild, and it is safe for long-term use, even in older adults.
12345Will 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.
Eligibility Criteria
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
I am between 21 and 65 years old.
I drink more than 14 (if male) or 7 (if female) alcoholic drinks weekly.
Exclusion Criteria
I am taking medication that cannot be mixed with diclofenac.
I am taking medication for schizophrenia, bipolar disorder, or similar conditions.
I am not pregnant, nursing, or willing to use birth control if I can have children.
I tested positive for COVID-19 and had symptoms in the last 3 months.
Participant Groups
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.
4Treatment groups
Active Control
Placebo Group
Group I: Diclofenac 50mgActive Control1 Intervention
In this arm participants will receive 50mg of Diclofenac
Group II: Diclofenac 75mgActive Control1 Intervention
In this arm participants will receive 75mg of Diclofenac
Group III: Diclofenac 100mgActive Control1 Intervention
In this arm participants will receive 100mg of Diclofenac
Group IV: PlaceboPlacebo Group1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Maryland Psychiatric Research CenterCatonsville, MD
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Who is running the clinical trial?
University of Maryland, BaltimoreLead Sponsor
References
Diclofenac sodium (Voltaren) and naproxen in the treatment of rheumatoid arthritis: a comparative double-blind study. [2019]In a double-blind, between-patient trial the efficacy and tolerability of two new non-steroid anti-inflammatory analgesics-diclofenac sodium (Voltaren) 50 mg b.i.d. and naproxen 250 mg b.i.d.-were compared in hospitalised patients with rheumatoid arthritis. Both drugs had a clearly positive effect on the duration of morning stiffness, bilateral grip strength, pain at rest, and pain on movement. No statistically significant difference between the two drugs was found with respect to clinical efficacy. Three patients treated with diclofenac sodium reported unwanted effects, as compared with seven patients receiving naproxen. These unwated effects led to premature discontinuation of the treatment in one patient on naproxen. Thus, although both drugs were well tolerated, it appeared that diclofenac sodium caused somewhat fewer unwanted effects.
Diclofenac. [2013]Diclofenac is the newest NSAID to be introduced to the United States. Extensive worldwide clinical studies with diclofenac have demonstrated its efficacy in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Its overall safety and efficacy is comparable to other available NSAIDs. The potential advantage of diclofenac is its short serum half-life but long synovial fluid concentration which enables twice daily dosing.
Worldwide safety experience with diclofenac. [2019]Worldwide use of diclofenac sodium since 1974 has yielded an extensive body of data on the safety of this drug. Documentation is derived from clinical trials, post-marketing surveillance, special studies, and spontaneous reports of adverse drug reactions from foreign countries. Comprehensive safety data from foreign studies show that diclofenac is safer and better tolerated than aspirin and is comparable in safety to ibuprofen and naproxen. Safety data from clinical trials in the United States, in which most patients received 150 mg daily of diclofenac, show that patients receiving diclofenac had lower rates of adverse reactions than patients receiving any of the comparative nonsteroidal anti-inflammatory drugs, except for naproxen at 500 mg daily. Special safety studies performed outside the United States address organ systems and patient groups of particular concern with nonsteroidal anti-inflammatory drugs, i.e., effects of diclofenac on gastrointestinal, renal, hepatic, and hemostatic systems; use in children and the elderly; and interactions with concomitant medications.
Worldwide clinical safety experience with diclofenac. [2019]Data from more than 100,000 patients in foreign and United States trials provide substantial evidence of diclofenac's safety and tolerability. Adverse experiences were infrequent and generally mild or transient. In United States short-term trials, the frequency and severity of side effects compared favorably with rates for placebo, aspirin, and other NSAIDs. The drop-out rate for therapeutic reasons (adverse effects or lack of efficacy) was lower for diclofenac than for any of the comparative treatments. In long-term trials, diclofenac has been taken safely for a year or more. The incidence of adverse experiences reported for older patients (greater than or equal to 65 years) treated with diclofenac did not generally differ from that reported for younger patients. No significant differences in the incidence of hepatic problems were detected between diclofenac and other active treatments in U.S. trials. Finally, foreign post-marketing data on adverse experiences show that diclofenac is one of the safest agents of its kind for the treatment of a broad range of rheumatic conditions.
[Voltaren--the gold standard]. [2013]In this article the advantages and the faults of diclofenac are described with short review of pharmacodynamic and pharmacokinetic properties and results of the recent clinical trials. The advantages of VOLTAREN are: efficacy in all NSAID indications, good tolerability, favourable COX-2/COX-1 ratio, the wide range of drug forms, long treatment experience and extremely acceptable cost-benefit ratio. Precaution in patients with risk is recommended.
The medical uses and side effects of etanercept with a focus on cutaneous disease. [2015]Etanercept is a dimeric fusion protein that has been approved for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, active ankylosing spondylitis and moderate to severe plaque psoriasis. It has been reported to be useful in other variants of psoriasis, Still's disease, recurrent aphthous ulcers, and a variety of rare cutaneous conditions. Its cutaneous side effects are rare and include injection site reactions, cutaneous lupus, and cutaneous vasculitis. Its systemic side effects are also rare and include induction or worsening of infections, lupus, multiple sclerosis, and congestive heart failure. Linkage to an increased risk of lymphoma is unclear. In short, etanercept is a promising medication with substantial benefits and use will probably increase in the future. This review surveys off-label uses and side effects of etanercept.
Baseline characteristics and patient reported outcome data of patients prescribed etanercept: web-based and telephone evaluation. [2021]The anti-TNF inhibitor, etanercept is administered as a once or twice weekly subcutaneous injection for the treatment of rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis (JIA). Limited data from the patients' perspective are available on the use of biologics in the treatment of these chronic conditions and this evaluation was designed to collect data from patients who had been prescribed etanercept for the first time. This manuscript describes the self-reported baseline characteristics and health-related quality of life of patients prior to treatment. Follow-up data will be reported separately.
Etanercept: a review of its use in autoimmune inflammatory diseases. [2022]With its approval more than 15 years ago, subcutaneous etanercept (Enbrel(®)) was the first biological disease-modifying antirheumatic drug (bDMARD) and the first tumour necrosis factor inhibitor to be approved for use in rheumatic diseases. Etanercept remains an important cost-effective treatment option in adult patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or plaque psoriasis, and in paediatric patients with juvenile idiopathic arthritis or plaque psoriasis. In all of these populations, etanercept (with or without methotrexate) effectively reduced signs and symptoms, disease activity and disability, and improved health-related quality of life, with these benefits sustained during long-term treatment. The safety profile of etanercept during short- and long-term treatment was consistent with the approved product labelling, with adverse events being of a predictable and manageable nature. The introduction of etanercept and other bDMARDs as therapeutic options for patients with autoimmune rheumatic diseases and spondyloarthropathies revolutionized disease management and these agents continue to have a central role in treatment strategies. This article reviews the extensive clinical experience with etanercept in these patient populations.
A novel electromechanical autoinjector, AutoTouch™, for self-injection of etanercept: real-world use and benefits. [2022]We assessed the ability of patients with autoimmune inflammatory diseases to successfully use the investigational AutoTouch™ reusable autoinjector as well as patient preference for AutoTouch™ versus the currently marketed single-use prefilled etanercept SureClick® autoinjector.
Pharmaceutical Approval Update. [2020]Lisinopril oral solution (Qbrelis) for the treatment of hypertension, heart failure, and acute myocardial infarction; etanercept-szzs (Erelzi) for multiple autoimmune disorders; and lumacaftor/ivacaftor (Orkambi) for cystic fibrosis.