NSAIDs for Menstrual Cramps

(NSAIDHEAL Trial)

Overseen By Kevin Hellman, PHD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Endeavor Health

Must be taking: NSAIDs

Must not be taking: Anticoagulants, Lithium, Diuretics, others

Disqualifiers: Chronic pain, GI bleeding, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 year

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether naproxen sodium, a common pain reliever, can reduce menstrual pain and potentially prevent long-term pelvic pain. Participants will take either naproxen sodium or a placebo to assess differences in pain relief. Over the course of a year, participants will track their symptoms and provide samples both at home and at the research site. Those who regularly experience painful periods and have consistent menstrual cycles might be suitable candidates. The trial aims to determine naproxen's effectiveness and identify factors that could predict its success in treating pain. As a Phase 4 trial, it focuses on an FDA-approved treatment, seeking to understand how naproxen sodium benefits a broader patient population.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking certain medications like anticoagulants, lithium, diuretics, and others listed in the exclusion criteria.

What is the safety track record for naproxen sodium?

Research shows that naproxen sodium is generally safe for treating menstrual cramps. Studies have found that at over-the-counter doses, naproxen effectively relieves pain and is well-tolerated. A meta-analysis, which combines results from multiple studies, identified it as a good option for managing painful periods. Participants who used naproxen for up to six months reported few side effects. This suggests that naproxen sodium can be a safe choice for many seeking relief from menstrual pain. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using naproxen sodium for menstrual cramps because it offers a promising approach to pain relief with an established nonsteroidal anti-inflammatory drug (NSAID) that could potentially provide more consistent results. Unlike other over-the-counter options, such as ibuprofen or standard acetaminophen, naproxen sodium has a longer duration of action, which could mean less frequent dosing and more sustained relief during the painful days of a menstrual period. Additionally, the inclusion of extended-release acetaminophen as a rescue medication provides a tailored approach to managing breakthrough pain, combining the strengths of both medications. This treatment regimen might offer an effective balance of sustained relief and immediate support when needed.

What is the effectiveness track record for naproxen sodium in treating menstrual cramps?

Research has shown that naproxen sodium, which participants in this trial may receive, effectively relieves menstrual pain. Studies have found it works better than acetaminophen for menstrual cramps, especially over 12 hours. A detailed review found that naproxen sodium significantly reduced pain for those with painful periods, outperforming a placebo. It is particularly effective for severe cramps, though less effective for mild cramps. Overall, the evidence supports its use as a reliable option for managing menstrual pain. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for menstruating adults with painful periods who may be at risk of developing chronic pelvic pain. Participants must be willing to take medication during their menstrual cycle, complete questionnaires and tests from home, provide urine and blood samples, and visit the research site twice in a year.

Inclusion Criteria

I experience painful periods.

Regular menstrual cycles (every 22-35 days)

Exclusion Criteria

My high blood pressure is hard to control.

I have had a stroke in the past.

I am allergic to NSAIDs or their ingredients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take naproxen sodium or placebo during several days of their menstrual period every month for 1 year. They also complete computer questionnaires and tests from home every 3 months, and at-home urine tests to measure hormones every few days for 1 year.

1 year

2 visits (in-person) over 1 year, multiple at-home activities

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of non-menstrual pelvic pain and chronic pelvic pain.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Naproxen Sodium

Trial Overview The study is testing if naproxen sodium (an NSAID) can treat menstrual cramps effectively and prevent long-term pelvic pain. It involves comparing naproxen sodium to a placebo over one year while monitoring participants' pain levels, hormone measurements, and sensitivity changes.

How Is the Trial Designed?

Group I: Active Drug Paradigm Active Control 2 Interventions

Participants in this arm will be given naproxen sodium (550mg) as the study treatment, along with extended release acetaminophen (650mg) as a rescue medication. Participants are instructed to take 1 dose of naproxen sodium every 12 hours during the first 48 hours of their menstrual period. If participants do not feel adequate pain relief within 2 hours of taking a dose of naproxen sodium, they can take 1 dose of acetaminophen; they can repeat this process again in another 2 hours if needed for pain relief. Participants are instructed to follow this regime during each menstrual period for 1-year. Participants will not know whether or not they have received naproxen sodium or placebo, but they will know that they have been give acetaminophen as an optional rescue medication.

Group II: Placebo Paradigm Placebo Group 2 Interventions

Participants in this arm will be given a placebo capsule that is visually identical to the active drug as the study treatment, along with extended release acetaminophen (650mg) as a rescue medication. Participants are instructed to take 1 dose of the placebo every 12 hours during the first 48 hours of their menstrual period. If participants do not feel adequate pain relief within 2 hours of taking a dose of the placebo, they can take 1 dose of acetaminophen; they can repeat this process again in another 2 hours if needed for pain relief. Participants are instructed to follow this regime during each menstrual period for 1-year. Participants will not know whether or not they have received naproxen sodium or placebo, but they will know that they have been give acetaminophen as an optional rescue medication.

Who Is Running the Clinical Trial?

Endeavor Health

Lead Sponsor

Trials

135

Recruited

742,000+

University of Oklahoma

Collaborator

Trials

484

Recruited

95,900+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a study involving 64 women with primary dysmenorrhea, naproxen sodium was found to be significantly more effective than placebo in reducing pain intensity and allowing women to continue their daily activities during menstrual cycles.

Only one participant experienced side effects from naproxen sodium, indicating that it is a safe option for managing dysmenorrhea, especially since it greatly reduced the number of women who had to stay home due to pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naproxen sodium in dysmenorrhea. Its influence in allowing continuation of work/school activities. Hanson, FW., Izu, A., Henzl, MR.[2013]

In a study of 34 women with premenstrual syndrome, naproxen sodium (550 mg twice daily) significantly reduced both menstrual and premenstrual pain compared to a placebo, demonstrating its efficacy in managing these symptoms.

The treatment also led to notable improvements in premenstrual behavioral changes, suggesting that alleviating pain can positively impact emotional well-being, confirming naproxen sodium as a safe and effective option for treating premenstrual syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naproxen sodium in the treatment of premenstrual symptoms. A placebo-controlled study. Facchinetti, F., Fioroni, L., Sances, G., et al.[2018]

In a randomized, double-blind study involving valdecoxib (20 mg and 40 mg) and naproxen sodium (550 mg) for treating menstrual pain in primary dysmenorrhea, both doses of valdecoxib provided significant pain relief compared to placebo, especially in the first 8 to 12 hours after dosing.

Valdecoxib demonstrated similar efficacy to naproxen sodium in managing menstrual pain, indicating it could be a viable alternative for women suffering from primary dysmenorrhea, and both doses were well tolerated by participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea. Daniels, SE., Talwalker, S., Torri, S., et al.[2019]

A single oral dose of 1100 mg of Naproxen-Sodium significantly reduced menstrual pain and uterine activity in 10 patients with dysmenorrhea, showing a strong efficacy (P < 0.001).

The treatment was well-tolerated with no reported side effects, suggesting it could be a safe option for managing dysmenorrhea, warranting further extensive trials to explore its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of naproxen-sodium on the intrauterine pressure and menstrual pain of dysmenorrheic patients. Csapo, AI., Pulkkinen, MO., Henzl, MR.[2019]

In a double-blind trial involving 32 women with dysmenorrhea, naproxen sodium significantly improved pain relief compared to placebo, with an average relief score of 13.7 versus 8.8 out of 18, indicating its efficacy in treating menstrual pain.

The study reported minimal side effects among participants, suggesting that naproxen sodium is a safe option for managing dysmenorrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium. Sande, HA., Salvesen, T., Izu, A.[2019]

Naproxen and naproxen sodium are effective non-steroidal anti-inflammatory drugs (NSAIDs) with various indications, but they can cause adverse reactions affecting the gastrointestinal tract, central nervous system, kidneys, liver, and blood.

Recent studies raise questions about the safety and recommendations for using these drugs, particularly in vulnerable populations like the elderly and pregnant women, highlighting the need for cautious prescribing practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naproxen: pharmacology and dental therapeutics. Roda, RS.[2022]

In a study involving 189 women with primary dysmenorrhea, naproxen sodium (440 mg) provided significantly greater pain relief compared to acetaminophen (1000 mg) over a 12-hour period, with a notable difference in total pain relief scores (p < 0.001).

Naproxen sodium not only reduced pain intensity more effectively than acetaminophen but was also rated as good-to-excellent by a higher percentage of participants (70.6% vs. 63.1%, p = 0.002), indicating its superior efficacy for menstrual pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant, long-lasting pain relief in primary dysmenorrhea with low-dose naproxen sodium compared with acetaminophen: a double-blind, randomized, single-dose, crossover study. Daniels, SE., Paredes-Diaz, A., An, R., et al.[2020]

In a clinical trial involving 20 patients with painful menstrual periods due to endometriosis, naproxen sodium provided complete or substantial pain relief in 83% of cases, compared to only 41% with placebo, demonstrating its efficacy (P = .008).

Naproxen sodium also reduced the need for additional pain relief, with only 5% of treated women requiring supplemental analgesics versus 36% in the placebo group (P = .002), and it was found to be safe with no significant side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naproxen sodium in dysmenorrhea secondary to endometriosis. Kauppila, A., Rönnberg, L.[2013]

In a double-blind cross-over study involving 57 healthy women, both ibuprofen and naproxen-sodium significantly reduced the severity of primary dysmenorrhea pain compared to baseline levels.

Ibuprofen provided greater pain relief than naproxen-sodium, indicating it may be a more effective option for treating menstrual pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibuprofen and naproxen-sodium in the treatment of primary dysmenorrhea: a double-blind cross-over study. Milsom, I., Andersch, B.[2019]

Naproxen sodium and naproxen have been shown to be effective analgesics for treating various obstetric and gynecologic pain conditions, including dysmenorrhea, postpartum pain, and pain from gynecologic surgery.

The literature review indicates that these compounds are useful in managing pain and inflammation associated with a wide range of gynecologic issues, highlighting their versatility as pain relief options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naproxen sodium for OB/GYN use, with special reference to pain states: a review. Edgren, RA., Morton, CJ.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31397597/

a double-blind, randomized, single-dose, crossover study Conclusions: A single, maximum non-prescription dose of naproxen sodium was more effective than acetaminophen over 12 h. Keywords: Acetaminophen; anti- ...

2. journals.lww.com journals.lww.com/md-journal/fulltext/2020/05080/efficacy_and_safety_of_over_the_counter_analgesics.8.aspx

Efficacy and safety of over-the-counter analgesics for primary As for efficacy outcomes, all the included analgesics except aspirin were more effective than placebo in treating dysmenorrhea [naproxen (OR 3.99, 95% CI 2.18– ...

3. aleve.com aleve.com/healthcare-professionals/efficacy-and-pain-guidelines/primary-dysmenorrhea

Primary Dysmenorrhea Pain Study and Guidelines A single maximum non-prescription dose of Aleve (naproxen sodium) provided more pain relief over 12 hours than acetaminophen for menstrual cramps due to ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291802800431

a pooled analysis of five studies Conclusion: When administered at OTC doses, naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/6571974/

Effects of naproxen sodium on menstrual prostaglandins and ... Symptomatically, naproxen sodium was most effective in alleviating severe menstrual cramps but had little effect on mild cramps.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7220209/

Efficacy and safety of over-the-counter analgesics for ... Our network meta-analysis showed that the OTCAs were well tolerated as a pain-relief option for dysmenorrhea over a period of 6 months. Our safety outcomes ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06861920

NSAID Use for Treating Dysmenorrhea and Preventing ... The goal of this clinical trial is to learn if NSAIDs (i.e. naproxen sodium) can treat menstrual pain and prevent the development of chronic pelvic pain in ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6953236/

Nonsteroidal anti‐inflammatory drugs for dysmenorrhoea - PMC The review found that NSAIDs appear to be very effective in relieving period pain. The evidence suggests that if 18% of women taking placebo achieve moderate or ...