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

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. ^{1 2 3 4 5}

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. ^{1 2 3 4 6}

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. ^{1 2 3 4 7}

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.

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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 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 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]

References

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

Ulcers of the small bowel associated with stomach-bypassing salicylates. [2019]

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

Salsalate for arthritis: a clinical evaluation. [2015]

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

An endoscopic comparison of the gastroduodenal injury seen with salsalate and naproxen. [2015]

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

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

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

Comparative study of salsalate and aspirin in osteoarthrosis of the hip or knee. [2019]

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

Reduced risk of NSAID gastropathy (GI mucosal toxicity) with nonacetylated salicylate (salsalate): an endoscopic study. [2015]

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

Comparison of salsalate and aspirin on mucosal injury and gastroduodenal mucosal prostaglandins. [2019]