Salsalate for Endometriosis

(Endo3/SA2 Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Penn State University

Must be taking: Oral contraceptives

Must not be taking: Cardiovascular medications

Disqualifiers: Diabetes, Hypertension, Pregnancy, others

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to better understand the underlying mechanisms associated with elevated cardiovascular disease risk in women with endometriosis, and to measure the effectiveness of emerging endometriosis treatments on outcomes specific to cardiovascular dysfunction. Epidemiologic data demonstrate a clear association between endometriosis, reproductive risk factors, inflammation and cardiovascular (CV) risk. Circulating factors, low-density lipoprotein (LDL) and oxidized LDL (oxLDL), are two of many biomarkers of cardiovascular and inflammatory disease of endometriosis. An important signaling mechanism through which circulating LDL and oxLDL act is the lectin-like oxidized LDL receptor (LOX-1). LOX-1 signal transduction functionally results in pronounced endothelial dysfunction, a hallmark of CV. The investigators hypothesis that one factor mediating the elevated risk of cardiovascular disease in endometriosis is systemic inflammation and activation of LOX-1 receptor mechanisms.

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.

What data supports the effectiveness of the drug salsalate for treating endometriosis?

While there is no direct evidence for salsalate's effectiveness in treating endometriosis, studies show it effectively reduces symptoms like pain and stiffness in arthritis patients, with 79% experiencing symptom relief. This suggests it may help with pain management in endometriosis as well.

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Is salsalate generally safe for human use?

Salsalate has been shown to be generally safe for human use, with fewer stomach-related issues compared to some other anti-inflammatory drugs like naproxen. However, it may cause side effects such as tinnitus (ringing in the ears) or hearing loss, and in rare cases, ulcers in the small bowel.

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How does the drug salsalate differ from other treatments for endometriosis?

Salsalate is unique because it is a nonacetylated salicylate that causes less stomach and intestinal damage compared to other similar drugs like aspirin and naproxen, making it potentially safer for long-term use. It also does not significantly inhibit prostaglandin synthesis, which may reduce the risk of gastrointestinal side effects.

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Eligibility Criteria

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.

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Pennsylvania State University University Park, PA

The Pennsylvania State University University Park, PA

Who Is Running the Clinical Trial?

Penn State University Lead Sponsor

References

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

Ulcers of the small bowel associated with stomach-bypassing salicylates. [2019] Ulcers of the small bowel are documented in a patient after intake of salsalate. Rapid clinical and endoscopic improvement occurred on discontinuation of administration of the drug. Endoscopic features suggested the direct effect of a tablet dissolving in the proximal part of the small bowel. To my knowledge, this is the first report of small-bowel ulcerations associated with the newer form of salicylates that bypass the stomach for their absorption.

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

Salsalate for arthritis: a clinical evaluation. [2015] In an open-label trial, 182 patients with common forms of arthritis were treated with 3 gm of salsalate daily (two 750-mg tablets twice daily) for 15 days. Before entering the study, these patients had received a wide variety of antiarthritic medications. Five indices of disease severity (pain, stiffness, joint swelling, limitation of motion, and disability) were evaluated before and after salsalate therapy, the incidence of side effects was tabulated before and after treatment, and patient compliance with the salsalate regimen was assessed. A reduction in disease symptoms was noted in 79% of the treated patients. Median improvement, measured on a summary index, was 47%. The incidence of side effects experienced with previous therapy was reduced by 65% during salsalate administration. Patient compliance with the regimen was greater than 95%. The findings show salsalate to be effective and safe in ameliorating the symptoms of arthritic disease. The convenient twice-daily dosage regimen makes this drug particularly suitable for chronic use.

3. Canada pubmed.ncbi.nlm.nih.gov

An endoscopic comparison of the gastroduodenal injury seen with salsalate and naproxen. [2015] Forty endoscopically normal healthy subjects were randomized to receive either BID salsalate (3500 mg/day) or BID naproxen (750 mg/day) for 14 days followed by repeat endoscopic examination. Gastroduodenal lesions were found in 55% (11/20) of the subjects taking naproxen, and 10% (2/20) of those taking salsalate (p = 0.002). Twenty-five percent (5/20) of the subjects taking naproxen and none of the subjects taking salsalate were noted to have severe gastric injury (p = 0.003). There was no difference between the 2 groups in subjective gastrointestinal system adverse experiences. Overall, 95% (19/20) of subjects taking salsalate reported at least 1 adverse experience compared with 60% (12/20) of those taking naproxen (p = 0.02). This was due primarily to the higher number of subjects taking salsalate reporting reversible tinnitus or hearing loss. There was no significant treatment difference in adverse experiences reported for any other organ system. The results of our study support previous observations in patients with rheumatoid arthritis that salsalate produces less gastroduodenal mucosal toxicity than the widely used antiinflammatory agent, naproxen.

4. England pubmed.ncbi.nlm.nih.gov

Relationship of plasma salicylate levels to pain relief with two different salicylates. [2019] In a preliminary open study of salsalate (3 g daily for 4 weeks) in 61 patients with rheumatoid arthritis or osteoarthrosis, it was found that although the drug produced satisfactory analgesia in 64% of patients, the incidence of side-effects was high (57% of patients): most were symptoms of salicylism and probably related to the high plasma salicylate levels achieved. In a second open study, 20 patients with osteoarthrosis were treated for 4 weeks with 250 mg diflunisal twice daily and then crossed over to salsalate (3 g daily) for a further 2 weeks. The results of subjective assessments of pain relief showed that both drugs produced satisfactory analgesia, and neither was associated with a significant level of gastro-intestinal bleeding. During the diflunisal treatment period there were no reports of salicylism, and plasma salicylate levels were very much lower than those measured after salsalate. The pain relieving effects of both drugs, assessed from patient preference for one or the other treatment, were unrelated to the plasma salicylate levels and it is suggested that plasma levels may have more relationship to the incidence of side-effects than with therapeutic effects.

5. England pubmed.ncbi.nlm.nih.gov

Comparative study of salsalate and aspirin in osteoarthrosis of the hip or knee. [2019] A short-term, double-blind controlled crossover study was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the effectiveness and tolerance of salsalate and aspirin. After a 1-week placebo washout period, patients received either 3 g salsalate per day or 3.6 g soluble aspirin per day for 2 weeks before being crossed over to the alternative treatment. Paracetamol was used as a rescue analgesic. The results of clinical assessments of pain, stiffness and sleep disturbance, using visual analogue scales, showed that salsalate produced a comparable clinical improvement to that with aspirin, and similar serum salicylate levels. Salsalate, however, was significantly superior to aspirin with regard to side-effects and faecal occult blood loss.

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

Reduced risk of NSAID gastropathy (GI mucosal toxicity) with nonacetylated salicylate (salsalate): an endoscopic study. [2015] This randomized, investigator-blinded, parallel group endoscopic study evaluated the effects of salsalate and naproxen on the gastroduodenal mucosa over a 3-month period in patients with RA. Using therapeutic doses of the drugs, 8 of 21 patients (38%) in the naproxen group had endoscopically shown active ulcers (seven patients) or diffuse erosions (one patient), whereas none of the 18 patients treated with salsalate (0%) had such lesions (P = .003). Five of the eight naproxen-treated patients with evidence of GI damage were asymptomatic at the time of endoscopic verification of their lesions. The most significant disadvantage of salsalate was its higher incidence of otologic problems accounting for six of the nine discontinuations with salsalate. However, the findings of this study suggest that patients receiving salsalate are at lower risk for developing significant gastropathy than those treated with naproxen. The relative benefit-to-risk ratio of salsalate indicates that this drug should be considered as a significant alternative NSAID therapy.

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

Comparison of salsalate and aspirin on mucosal injury and gastroduodenal mucosal prostaglandins. [2019] The effects of a 7.5-day course of orally administered salsalate (3.0 g/day), aspirin (3.9 g/day), or placebo on gastroduodenal mucosal injury, mucosal prostaglandin content, and plasma prostaglandin concentrations in healthy, asymptomatic human volunteers were examined. Mean serum salicylate concentrations after these doses of salsalate and aspirin were nearly identical (approximately 15 mg/dL). When the gastroduodenal mucosa was assessed endoscopically 1 hour after the final dose of medication, there was minimal mucosal injury in placebo-treated or salsalate-treated subjects and considerable injury in the stomach and duodenum of aspirin-treated subjects (P less than 0.001, aspirin vs. salsalate or placebo). In both the stomach and duodenum, aspirin lowered mucosal prostaglandin F2a and E2 content by greater than 90% (P less than 0.001), whereas salsalate produced no significant change. Aspirin also lowered plasma prostaglandin F2a concentrations by 58% +/- 6%, whereas salsalate lowered them by only 11% +/- 9% (P less than 0.001). Thus, the nonacetylated salicylate, salsalate, produced much less gastroduodenal mucosal damage than aspirin at equivalent serum salicylate concentrations, possibly because salsalate did not inhibit mucosal prostaglandin synthesis.