Salsalate for Endometriosis

(Endo3/SA2 Trial)

Recruiting at 1 trial location

Overseen By Susan Slimak, RN

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Penn State University

Must be taking: Oral contraceptives

Must not be taking: Cardiovascular medications

Disqualifiers: Diabetes, Hypertension, Pregnancy, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Salsalate, a non-steroidal anti-inflammatory drug, might manage cardiovascular risks in women with endometriosis, a condition where tissue similar to the uterine lining grows outside the uterus. Researchers examine how Salsalate affects heart health markers in these women. The trial includes two groups: one taking Salsalate and another taking a placebo (a non-active pill) for five days. Women diagnosed with endometriosis in the past five years who do not use nicotine products may be suitable for this study. As an Early Phase 1 trial, this research focuses on understanding how Salsalate 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 medications that could affect blood vessel control, like those for heart conditions or insulin sensitizing drugs. If you're on such medications, you would need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that salsalate, an oral medication, resembles other drugs in its group and may carry some risks. Studies indicate that salsalate can affect small blood vessels, though it might not alter the function of larger vessels. This is important to consider.

Warnings exist about potential serious side effects on the heart and stomach, such as heart attacks or strokes. Anyone considering this treatment should discuss these risks with a healthcare provider. The FDA has not approved salsalate as safe and effective for general use, suggesting that its safety profile may not be fully understood. ^{1 2 3 4 5}

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

Unlike the standard treatments for endometriosis, which often include hormonal therapies or surgeries, salsalate is unique because it is an anti-inflammatory drug. Most treatments for endometriosis aim to regulate hormones or remove tissue. In contrast, salsalate works by reducing inflammation, which could potentially alleviate pain and other symptoms more quickly. Researchers are excited about salsalate because it offers a non-hormonal option, which may have fewer side effects and provide relief in just a few days.

What evidence suggests that Salsalate might be an effective treatment for endometriosis?

This trial will compare the effects of Salsalate with a placebo in participants with endometriosis. Research suggests that Salsalate can reduce pain and stiffness in conditions similar to endometriosis. However, direct proof of its effectiveness for endometriosis itself is not yet available. Studies have found that Salsalate might affect the function of small blood vessels in women with endometriosis, but it does not seem to impact larger blood vessels. Researchers are investigating its potential to lower inflammation, which might relate to heart health risks in women with endometriosis. While early results are encouraging, more research is needed to confirm Salsalate's benefits for endometriosis. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy women aged 18-45, either on birth control or with regular menstrual cycles, who have been diagnosed with endometriosis by laparoscopy within the last 5 years. It's not for those with abnormal liver function, drug use, skin allergies including latex and salsalate, gastrointestinal bleeding history, diabetes (HbA1C ≥6.5%), high blood pressure (>140/90), pregnancy or breastfeeding.

Inclusion Criteria

You can use birth control during the study.

I am a healthy woman, 18-45, using birth control or have regular periods every 26-34 days.

I can take Tylenol for acute pain.

Exclusion Criteria

BP>140/90

My liver isn't working properly.

You are pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 3000 mg/day salsalate or placebo for 5 days to assess cardiovascular and inflammatory biomarkers

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of vascular conductance and hormone levels

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Salsalate Pill

Trial Overview The study aims to understand how endometriosis may increase heart disease risk by looking at inflammation and blood vessel health. Women will take either a Salsalate pill or a placebo to see if it affects cardiovascular biomarkers like LDL cholesterol and its role in activating certain receptors linked to heart disease.

How Is the Trial Designed?

Group I: Salsalate Experimental Treatment 1 Intervention

3000 mg/day salsalate (1500 mg twice daily) for 5 days

Group II: Placebo Placebo Group 1 Intervention

1 capsule contain microcrystalline cellulose filler (twice daily) for 5 days

Salsalate Pill is already approved in United States, Canada for the following indications:

Approved in United States as Disalcid for:

• Rheumatoid arthritis
• Osteoarthritis
• Pain relief

Approved in Canada as Salflex for:

• Rheumatoid arthritis
• Osteoarthritis
• Pain relief

Who Is Running the Clinical Trial?

Penn State University

Lead Sponsor

Trials

380

Recruited

131,000+

Published Research Related to This Trial

In a study of 40 healthy subjects, salsalate (3500 mg/day) resulted in significantly fewer gastroduodenal lesions (10%) compared to naproxen (750 mg/day), which caused lesions in 55% of participants (p = 0.002).

While 95% of salsalate users reported at least one adverse experience, the majority were reversible tinnitus or hearing loss, and overall, salsalate showed less severe gastric injury compared to naproxen, which had a 25% incidence of severe injuries (p = 0.003).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An endoscopic comparison of the gastroduodenal injury seen with salsalate and naproxen. Lanza, F., Rack, MF., Doucette, M., et al.[2015]

A patient developed small bowel ulcers after taking salsalate, a type of salicylate medication, which is known to be absorbed without affecting the stomach.

The ulcers improved quickly after stopping the medication, suggesting that salsalate may have a direct harmful effect on the small bowel when it dissolves there. This is the first report linking this newer form of salicylate to such ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ulcers of the small bowel associated with stomach-bypassing salicylates. Souza Lima, MA.[2019]

In a study involving healthy volunteers, a 7.5-day course of salsalate (3.0 g/day) caused minimal mucosal injury compared to significant damage observed with aspirin (3.9 g/day), highlighting salsalate's safer profile for the gastroduodenal mucosa.

Salsalate did not significantly reduce mucosal prostaglandin levels, unlike aspirin, which decreased these levels by over 90%, suggesting that salsalate's reduced mucosal damage may be due to its lack of inhibition on prostaglandin synthesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of salsalate and aspirin on mucosal injury and gastroduodenal mucosal prostaglandins. Cryer, B., Goldschmiedt, M., Redfern, JS., et al.[2019]

In a trial with 182 arthritis patients, 79% experienced a reduction in disease symptoms after taking 3 grams of salsalate daily for 15 days, with a median improvement of 47%.

Salsalate not only effectively alleviated arthritis symptoms but also reduced the incidence of side effects from previous treatments by 65%, and had a high patient compliance rate of over 95%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salsalate for arthritis: a clinical evaluation. McPherson, TC.[2015]

In a study of 39 patients with rheumatoid arthritis over 3 months, naproxen was associated with a significantly higher incidence of gastroduodenal ulcers and erosions (38%) compared to salsalate, which showed no such lesions (0%).

Despite a higher rate of otologic problems leading to discontinuation, salsalate presents a lower risk of gastrointestinal damage compared to naproxen, suggesting it could be a safer alternative NSAID for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced risk of NSAID gastropathy (GI mucosal toxicity) with nonacetylated salicylate (salsalate): an endoscopic study. Roth, S., Bennett, R., Caldron, P., et al.[2015]

In a study involving 20 patients with osteoarthrosis, salsalate was found to provide similar pain relief and improvement in stiffness and sleep disturbance as aspirin, indicating comparable efficacy.

Salsalate demonstrated a significantly better safety profile than aspirin, with fewer side effects and less faecal occult blood loss, making it a potentially safer alternative for managing osteoarthrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of salsalate and aspirin in osteoarthrosis of the hip or knee. Liyanage, SP., Tambar, PK.[2019]

In a study of 61 patients with rheumatoid arthritis or osteoarthrosis, salsalate provided satisfactory pain relief for 64% of patients, but had a high side-effect rate of 57%, likely due to elevated plasma salicylate levels.

A follow-up study with 20 patients showed that diflunisal, at a lower dose, also provided effective pain relief without significant side effects or salicylism, suggesting that lower plasma salicylate levels may reduce side effects while maintaining therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship of plasma salicylate levels to pain relief with two different salicylates. Hicklin, JA.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40047802/

Salsalate negatively impacts microvascular function in women ... Salsalate treatment impairs vasodilation in the cutaneous microcirculation in women with endometriosis through non-NO-dependent mechanisms.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12107711/

Salsalate Negatively Impacts Microvascular Function in ... Our results show that oral salsalate treatment negatively impacts microvascular function but does not alter macrovascular function.

3. withpower.com withpower.com/trial/early-phase-1-endometriosis-2022-c3176?condition=endometriosis&hasNoPlacebo=false&overallStatus=Recruiting

Salsalate for Endometriosis (Endo3/SA2 Trial) While there is no direct evidence for salsalate's effectiveness in treating endometriosis, studies show it effectively reduces symptoms like pain and stiffness ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05069740

Study Details | NCT05069740 | Endometriosis and ... The purpose of this study is to better understand the underlying mechanisms associated with elevated cardiovascular disease risk in women with endometriosis ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2589004224006096

Identifying therapeutic candidates for endometriosis ... However, these treatments are often ineffective, with nearly 19% of patients experiencing no reduction in pain and up to 59% having remaining ...

6. drugs.com drugs.com/pro/salsalate.html

Salsalate: Package Insert / Prescribing Information Salsalate tablets, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/020353s036lbl.pdf

This label may not be the latest approved by FDA. For current ... WARNING: RISK OF SERIOUS CARDIOVASCULAR AND. GASTROINTESTINAL EVENTS. See full prescribing information for complete boxed warning.

8. rxlist.com rxlist.com/disalcid-drug.htm

Disalcid (Salsalate): Side Effects, Uses, Dosage, ... Pregnancy Category C: Salsalate and salicylic acid have been shown to be teratogenic and embryocidal in rats when given in doses 4 to 5 times the usual human ...

9. webmd.com webmd.com/drugs/2/drug-8704/salsalate-oral/details

Salsalate: Uses, Side Effects, Interactions, Pictures, ... Note: The Food and Drug Administration (FDA) has not found this medicine to be safe and effective, and the label is not approved by the FDA.