NSAIDs for Menstrual Cramps

(NSAID-HEAL 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

Trial Summary

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 data supports the effectiveness of the drug Naproxen Sodium for menstrual cramps?

Research shows that Naproxen Sodium significantly reduces menstrual pain and helps women continue their daily activities compared to a placebo. In studies, women taking Naproxen Sodium reported greater pain relief and fewer disruptions to work or school due to menstrual cramps. ^{1 2 3 4 5}

Is naproxen sodium safe for treating menstrual cramps?

Naproxen sodium is generally considered safe for treating menstrual cramps, as studies show no significant side effects in patients using it for this purpose. ^{3 4 5 6 7}

How does the drug naproxen sodium differ from other treatments for menstrual cramps?

Naproxen sodium is unique because it provides significant and long-lasting pain relief for menstrual cramps compared to acetaminophen, and it is effective in both primary dysmenorrhea and dysmenorrhea related to endometriosis. It works by reducing inflammation and pain, and is more effective than acetaminophen over a 12-hour period. ^{5 6 8 9 10}

What is the purpose of this trial?

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 menstruating adults with painful periods. The main questions it aims to answer are: * Can non-menstrual pelvic pain reduction be predicted by menstrual pain response to NSAIDs? * Will participants with the largest reductions in multi-site sensitivity following NSAID therapy have the largest reductions in non-menstrual pelvic pain? Researchers will compare naproxen sodium to a placebo (a look-alike substance that contains no drug) to see if naproxen sodium works to treat painful periods. Participants will: * Take naproxen sodium or placebo during several days of their menstrual period every month for 1 year. * Complete computer questionnaires and tests from home every 3 months. * Complete at-home urine tests to measure hormones every few days for 1-year. * Use a pin-prick to collect a small spot of blood, and use a pad or tampon to collect a sample of menstrual blood, and bring it to the research site twice over a 1-year period. * Come to the research site twice over a 1-year period to complete sensory assessments and undergo a blood draw. The major goal of the study is to develop a multivariable statistical model (see https://grants.nih.gov/grants/guide/rfa-files/RFA-NS-24-021.html ) describing the factors that effectiveness of pain medication and risk for chronic pain

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

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

Naproxen sodium in dysmenorrhea. Its influence in allowing continuation of work/school activities. [2013]

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

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

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

Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea. [2019]

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

The effect of naproxen-sodium on the intrauterine pressure and menstrual pain of dysmenorrheic patients. [2019]

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

Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium. [2019]

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

Naproxen sodium in dysmenorrhea secondary to endometriosis. [2013]

7. Canada pubmed.ncbi.nlm.nih.gov

Naproxen: pharmacology and dental therapeutics. [2022]

8. England 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. [2020]

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

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

Naproxen sodium in the treatment of premenstrual symptoms. A placebo-controlled study. [2018]