Topical Diclofenac for Headaches

(DITCH Trial)

Overseen By Cristian Villegas, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Loma Linda University

Must not be taking: Dual antiplatelets, Opioids

Disqualifiers: Intracranial tumors, Cervical procedures, Fibromyalgia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a topical gel called diclofenac can reduce headaches linked to neck pain. Participants will have either the diclofenac gel or a placebo (a harmless substance) applied to their neck four times a day for two weeks. The researchers aim to determine if the diclofenac gel is more effective than the placebo in easing headache pain and its impact on daily life. Suitable candidates have headaches related to neck problems and are currently hospitalized at Loma Linda East Campus Rehabilitation Hospital. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the chance to contribute to potentially groundbreaking treatment advancements.

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

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on dual antiplatelet therapy or have certain conditions like chronic pain managed with continuous opioids.

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

Research has shown that diclofenac gel is usually safe when applied to the skin. In previous studies, many people used it without major problems. Some might experience mild side effects like skin irritation, dryness, or redness at the application site. These side effects are generally not serious and often resolve on their own.

Serious side effects are rare. However, some individuals might feel dizzy, nauseous, or develop a headache. These symptoms are uncommon but important to mention.

Diclofenac gel has already been approved for other uses, indicating its well-established safety. This suggests that the gel is safe for most people. Always consult a healthcare professional if any concerning symptoms arise. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for headaches?

Unlike the standard pills or injections used for headaches, Diclofenac Gel offers a unique topical delivery method. This gel is applied directly to the skin on the neck, which could potentially reduce systemic side effects often seen with oral medications. Researchers are excited about this approach because it targets pain directly and may offer quicker relief, making it a promising alternative for those who struggle with taking oral medications.

What evidence suggests that topical diclofenac gel might be an effective treatment for headaches?

Research shows that diclofenac gel effectively reduces pain and swelling. It is commonly used for arthritis pain because it works directly at the application site. Studies have found that this gel eases pain by reducing swelling and stiffness in joints. In this trial, some participants will receive diclofenac gel applied to the neck to investigate its potential to lower inflammation and pain signals that cause headaches. Although its use for headaches is still under investigation, its success in relieving other types of pain makes it a promising option. ^{2 6 7 8 9}

Who Is on the Research Team?

Duc Tran, MD, PhD

Principal Investigator

Loma Linda University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-90 who are hospitalized with cervicogenic headaches, can consent for themselves, and speak English or Spanish. Excluded are those on chronic opioid regimens, pregnant women, patients with fibromyalgia or cervical spine procedures history, primary headache from intracranial pathology, known diclofenac sensitivity, recent nerve blocks or steroid injections.

Inclusion Criteria

I have headaches due to a neck condition.

Hospitalized at Loma Linda East Campus Rehabilitation Hospital

Subject must be able to consent for themselves

Exclusion Criteria

I was discharged from acute rehab in less than 14 days.

I haven't had nerve blocks in the last 4 weeks or steroid injections in the last 6 months.

My headaches are caused by a brain tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Nursing staff apply 2 grams of diclofenac 1% gel or petroleum jelly topically to the posterior cervical region four times daily for 14 days. Surveys and metabolic panels are conducted at baseline, day 7, and day 14.

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diclofenac Gel

Trial Overview The study tests the effectiveness of diclofenac gel versus petroleum jelly in treating cervicogenic headaches. Participants will apply either diclofenac gel or petroleum jelly to their neck four times daily. Their headache severity before and after treatment will be measured using surveys.

How Is the Trial Designed?

Group I: Diclofenac Gel Experimental Treatment 1 Intervention

Nursing staff will apply 2 grams of diclofenac 1% gel topically to the posterior cervical region of the subject four times daily for 14 days. A questionnaire consisting of a Numeric Assessment Scale (NAS) and Headache Impact Test (HIT-6) will be administered at baseline (day 1), day 7, and at the study conclusion (day 14). A complete metabolic panel will obtained on day 0 and on day 14.

Group II: Control Placebo Group 1 Intervention

Nursing staff will apply a petroleum gel based compound topically to the posterior cervical region of the subject four times daily for 14 days. A questionnaire consisting of a Numeric Assessment Scale (NAS) and Headache Impact Test (HIT-6) will be administered at baseline (day 1), day 7, and at the study conclusion (day 14). A complete metabolic panel will obtained on day 0 and on day 14.

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

Approved in United States as Voltaren for:

• Osteoarthritis
• Actinic keratosis
• Pain
• Inflammation

Approved in European Union as Voltaren for:

• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis
• Pain
• Inflammation

Approved in Canada as Voltaren for:

• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis
• Pain
• Inflammation

Who Is Running the Clinical Trial?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Published Research Related to This Trial

A 0.1% diclofenac-Na Emulgel significantly alleviated pain and reduced symptoms like erythema and oedema in sunburned skin, showing efficacy when applied 6 and 10 hours after UV exposure.

A single application of the gel provided pain relief within 2 hours and maintained symptom reduction for up to 48 hours, demonstrating its effectiveness as a treatment for sunburn.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclofenac-Na gel is effective in reducing the pain and inflammation associated with exposure to ultraviolet light - results of two clinical studies. Kienzler, JL., Magnette, J., Queille-Roussel, C., et al.[2013]

The topical diclofenac epolamine (DHEP) patch provides significant pain relief and improved function for various conditions, including minor injuries and osteoarthritis, while minimizing systemic side effects due to low absorption.

The addition of heparin in the DHEP+H patch enhances its effectiveness without compromising safety, making it a reliable option for treating localized mild-to-moderate pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclofenac epolamine topical patch for the treatment of pain. Affaitati, G., Giamberardino, MA., Lapenna, D., et al.[2019]

Solaraze gel, which contains 3% diclofenac, has been used since 2001 as a topical treatment for actinic keratoses and is commonly utilized in dermatology.

While undesirable effects from Solaraze gel are considered rare, they can include skin reactions such as pruritus, paresthesia, and contact dermatitis, with recent reports highlighting cases of contact dermatitis linked to diclofenac and other allergens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photoallergic contact dermatitis from topical diclofenac in Solaraze gel. Kowalzick, L., Ziegler, H.[2013]

Topical diclofenac solution (1.5% w/w) significantly improves pain and physical function in patients with osteoarthritis of the knee compared to placebo, based on trials lasting 4 to 12 weeks.

It is as effective as oral diclofenac (150 mg/day) for treating osteoarthritis symptoms, with fewer gastrointestinal side effects and better overall tolerance, though dry skin at the application site was a common issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical diclofenac solution. Moen, MD.[2021]

Topical NSAIDs, like diclofenac sodium 1% gel, provide effective pain relief for osteoarthritis (OA) with less risk of serious side effects compared to oral NSAIDs, making them a preferred option for patients with mild-to-moderate OA.

Clinical trials indicate that diclofenac sodium 1% gel offers significant analgesia with a low incidence of systemic adverse events, supporting its use as a safe and effective treatment for OA in the United States.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical therapy for osteoarthritis: clinical and pharmacologic perspectives. Altman, R., Barkin, RL.[2013]

Topical diclofenac diethylamine (DDEA) 2.32% gel applied twice daily significantly reduced pain on movement in patients with acute ankle sprain, with a reduction of 49.1 mm compared to 25.4 mm in the placebo group by day 5 (P < 0.0001).

DDEA gel was well tolerated and led to a significant reduction in ankle swelling and improved treatment satisfaction, with over 70% of DDEA patients experiencing at least a 50% reduction in pain compared to only 21% in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of diclofenac diethylamine 2.32% gel in acute ankle sprain. Predel, HG., Hamelsky, S., Gold, M., et al.[2013]

In a study of 467 adults using over-the-counter Voltaren gel (diclofenac), participants reported a significant reduction in pain severity, improving by an average of 1.2 points on a scale of 0 to 10 after 12 weeks of treatment.

The majority of users, particularly those aged 65 and older, showed high satisfaction with the treatment and rarely switched to other topical therapies, indicating that Voltaren gel is a well-tolerated option for managing musculoskeletal pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' experience and utilization patterns of diclofenac gel in Germany: a real-world study with a prospective longitudinal survey and a retrospective analysis of pharmacy data. Maihöfner, C., de Haas, A., Sethi, V., et al.[2023]

In a study involving 32 patients with filamentary keratitis due to secondary Sjögren's syndrome, diclofenac sodium, 0.1%, demonstrated a significantly faster improvement in clinical symptoms compared to sodium chloride, 5%.

Both treatments were effective in eliminating filaments, and no significant adverse effects were reported, indicating that diclofenac sodium is a safe option for treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclofenac sodium, 0.1% (Voltaren Ophtha), versus sodium chloride, 5%, in the treatment of filamentary keratitis. Avisar, R., Robinson, A., Appel, I., et al.[2019]

In a study of 10 patients with significant psoriatic arthritis, diclonate P (sodium diclofenac) showed high clinical effectiveness, with 9 patients preferring it over previously used nonsteroidal anti-inflammatory drugs.

The treatment led to improvements in 10 out of 12 evaluated symptoms, with 7 showing significant improvement, and it was well-tolerated, causing only mild gastralgia in one patient, without adverse effects on psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of diclonate P in psoriatic arthritis]. Burdeĭnyĭ, AP.[2013]

In a clinical trial involving 172 subjects with first-degree sunburn, diclofenac-Na 0.1% gel significantly reduced pain intensity and erythema compared to a placebo gel, with effects noticeable within hours and peaking at 30 hours post-application.

The treatment was well-tolerated, with only mild and infrequent side effects reported, indicating that diclofenac-Na gel is a safe option for managing pain and discomfort from sunburn.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of low-dose diclofenac sodium 0.1% gel for the symptomatic relief of pain and erythema associated with superficial natural sunburn. Magnette, J., Kienzler, JL., Alekxandrova, I., et al.[2013]

Citations

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Anti-Inflammatory Creams for Pain Relief Topical anti-inflammatory creams can reduce swelling and pain caused by many health conditions and injuries. Voltaren (diclofenac) gel, capsaicin cream, and ...

2. mayoclinic.org mayoclinic.org/drugs-supplements/diclofenac-topical-application-route/description/drg-20063434

Diclofenac (topical application route) - Side effects & dosage Diclofenac is used to treat pain and other symptoms of arthritis of the joints (eg, osteoarthritis), such as inflammation, swelling, stiffness, and joint pain.

3. walmart.com walmart.com/ip/Voltaren-Arthritis-Pain-Gel-for-Powerful-Topical-Arthritis-Pain-Relief-No-Prescription-Needed-5-29-oz-150-g-Each/2098211207

Voltaren Arthritis Pain Relief Gel, 5.29 oz, Topical NSAID ... Containing the effective medicine diclofenac sodium, this topical NSAID (nonsteroidal anti-inflammatory drug) targets pain directly at the site for powerful ...

4. amazon.com amazon.com/Voltaren-Topical-Arthritis-Relief-Multi/dp/B089P2D6W1

Voltaren Arthritis Pain Gel, 12.34 Ounces 5.3 OZ2 Plus ... Voltaren Arthritis Pain Gel for Powerful Topical Arthritis Pain Relief with Diclofenac - NEW Easy Open Cap - 100 g x 2 · Voltaren Arthritis Pain Gel for ...

5. voltaren.ca voltaren.ca/en/products/topical-gels/

How Voltaren gel works and how to use it for pain relief Voltaren gels are designed to beat acute pain due to muscle & joint injury with a dual action: Relieving pain; Fighting inflammation. Woman using Voltaren Long ...

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Diclofenac topical (Voltaren) - Uses, Side Effects, and More What are the serious side effects of topical diclofenac? · Sudden severe headache · Chest pain · Dizziness or confusion · Trouble breathing · Nausea ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2000/21005lbl.pdf

Solaraze (diclofenac sodium) Gel, 3% w/w Prescribing ... These data indicate that systemic ... Of the 423 patients evaluable for safety in adequate and well-controlled trials, 211 were treated with Solaraze.

8. northamerica.covetrus.com northamerica.covetrus.com/Content/SDS/073221.pdf

Diclofenac sodium topical gel 1%w/w Date of Issue : 05.04. ... Inhalation. : Inhalation causes severe irritation to the respiratory tract. Symptoms of overexposure include headache, dizziness, nausea, shortness of breath.

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Safety of Topical Non-steroidal Anti-Inflammatory Drugs in ... In fact, the data showed a reduced odds of nervous system disorders (− 40%), mainly headache, with ketoprofen compared with placebo (OR 0.60, 95% CI 0.41–0.88).