Whether you’re a cop on the job or a grandparent playing with your grandkids, interrupting your day to visit the bathroom 30 to 40 times is exasperating. Frequent and painful urination are symptoms of interstitial cystitis, but the chronic painful bladder condition can present with a wide range of symptoms, often with varying severity.

“When someone presents with bladder pain or pelvic pain of unspecified origin, the clinician rules out known causes like injury or urinary tract infection,” said Stephen Walker, a regenerative medicine researcher at Wake Forest University who leads a new clinical trial for aloe vera as an interstitial cystitis treatment. “What they're left with is a bladder pain disorder of unspecified origin. Therein lies the challenge for diagnosing and also treating this population.”

Interstitial cystitis affects both men and women, but it is more common in women. The latest epidemiological data indicate that 2.7% to 6.5% of women in the United States have interstitial cystitis symptoms (1). With the need to urinate often, patients often cannot sleep through the night, which completely disrupts their lives. Patients with severe interstitial cystitis often qualify for disability benefits because the condition is so debilitating.

There is currently no single treatment that works for all interstitial cystitis patients, and many of the available therapeutics have severe side effects. In a new clinical trial, scientists at Wake Forest University will test the safety and efficacy of a highly concentrated aloe vera pill developed by the company Desert Harvest to relieve interstitial cystitis symptoms. The researchers hope that the aloe vera pill will give patients a side effect-free treatment option for this difficult-to-treat condition.

The heterogeneity of interstitial cystitis symptoms suggests that the condition may have multiple underlying causes. Patients may have a physical problem with their bladder, like a breakdown in the protective glycosaminoglycan (GAG) molecules that line the bladder walls, or they may have a systemic nerve disorder that leads to feeling the need to urinate more often, for example.

“I try to focus on trying to address whatever is the most bothersome symptom for that particular patient,” said Lenore Ackerman, a urologist at the University of California, Los Angeles who treats interstitial cystitis patients and is not associated with the clinical trial.

Urologists often try oral medications such as amitriptyline, which is an antidepressant but can be used to treat pain, or the immunosuppressive drug cyclosporine. But drugs like cyclosporine can have serious side effects on kidney function, and amitriptyline can make people feel sedated or sleepy. In the face of these side effects, there is also no guarantee that these treatments will work for a particular patient.

“A lot of these therapies do have some side effects, and they take some time to work. It can be very frustrating for patients,” Ackerman explained. “The problem is the side effects come first, and the effect comes a little bit later.”

Clinicians also try treatments delivered directly to the bladder via a bladder instillation, pelvic floor physical therapy, and dietary changes to treat interstitial cystitis. However, like amitriptyline and cyclosporine, most of these treatments have not been well-studied for their effect on interstitial cystitis specifically, so clinicians use them off-label.

While there is one FDA-approved treatment for interstitial cystitis called pentosan polysulfate sodium (Elmiron), clinicians hesitate to prescribe it due to its severe side effects like hair loss and potential macular degeneration (2). In fact, Johnson and Johnson, the company that makes Elmiron, is facing a series of class action lawsuits due to Elmiron’s maculopathy side effect.

“We don’t really have any great tried and true options for patients. A lot of it is just trying a bunch of different things and seeing what works,” Ackerman said.

But in the course of their clinical work, urologists, including Ackerman, have noticed that many patients talk about the relieving effects of aloe vera. In fact, survey data from interstitial cystitis patients taking aloe vera and results from Desert Harvest’s small 1995 clinical trial using aloe vera to treat interstitial cystitis symptoms indicate that aloe vera effectively treats some patients (3, 4).

Heather Florio, the CEO of Desert Harvest, has heard from many interstitial cystitis patients that aloe vera helped them get their lives back to normal. “We had a middle school girl, and her mother had made a seat like a bed on the toilet,” Florio said. “She started taking the aloe, and she got to start being a teenage girl. She got to go back to school, and she didn't have to sleep on the toilet. We get to hear all of these amazing, wonderful stories all the time.”

The Desert Harvest team hopes that their new, larger clinical trial of their aloe vera formulation with Wake Forest University will provide additional scientific evidence in support of the treatment for interstitial cystitis.

“We're working towards getting it as an FDA approved drug now so that people can have better access to it, and [it can] be a first line treatment,” said Florio.

Scientists are not sure why aloe vera relieves some interstitial cystitis symptoms, but they think it may be due to the plant’s richness in GAG molecules, the same molecules that form the protective lining of the bladder. By providing a concentrated source of natural GAG molecules, theoretically aloe vera may help rebuild the protective GAG layer that can be damaged in interstitial cystitis patients.

In addition to being highly concentrated, Desert Harvest’s aloe vera formulation also removes the anthraquinone molecules naturally present in aloe vera. Long-term exposure to anthraquinones has been associated with an increased risk for colon cancer (5), so its removal makes the company’s aloe vera capsule safer than other formulations for long-term, high-dosage use.

The researchers plan to begin the phase I clinical trial soon with thirty patients, and they hope to have data to share in mid to late 2022.

Walker hopes that future phases of the trial with larger cohorts of patients will help scientists identify the clinical differences between subsets of interstitial cystitis patients to determine who will respond best to aloe vera treatment.

Ackerman is looking forward to seeing the results of the trial. “Wouldn't it be great if we could give people some relief without compromising their quality of life?” she asked. “That's kind of our holy grail in the treatment of this condition, and I love this group for trying to really approach this scientifically to see if we can add this in as something meaningful to offer our patients.”

References

1. Konkle, K.S. et al. Comparison of an Interstitial Cystitis/Bladder Pain Syndrome Clinical Cohort With Symptomatic Community Women From the RAND Interstitial Cystitis Epidemiology Study. J Urol. 187, 508-512 (2012).
2. Shah, R. et al. Disease Course in Patients With Pentosan Polysulfate Sodium–Associated Maculopathy After Drug Cessation. JAMA Ophthalmol 138, 894-900 (2020).
3. O’Hare, P.G. et al. Interstitial cystitis patients’ use and rating of complementary and alternative medicine therapies. Int Urogynecol J 24, 977-982 (2013).
4. Findings reported by Desert Harvest. [Accessed December 2021]. Available at: https://www.desertharvest.com/physicians/documents/DH162.pdf
5. Citronberg, J.S. et al. Laxative type in relation to colorectal cancer risk. Annals of Epidemiology 28, 739-741 (2018).