Efficacy of the Natural Clay, Calcium Aluminosilicate Anti-Diarrheal, in Reducing Medullary Thyroid Cancer-Related Diarrhea and Its Effects on Quality of Life: A Pilot Study

Abstract

Introduction: Medullary thyroid cancer (MTC)-related diarrhea can be debilitating, reduces quality of life (QOL), and may be the only indication for initiating systemic therapy. Conventional antidiarrheal drugs are not always helpful and may have side effects. Calcium aluminosilicate antidiarrheal (CASAD), a natural calcium montmorrilonite clay, safely adsorbs toxins and inflammatory proteins associated with diarrhea. It was hypothesized that CASAD would reduce the severity of diarrhea and improve QOL in MTC patients.

Methods: This was a prospective pilot trial (NCT01739634) of MTC patients not on systemic therapy with self-reported diarrhea of three or more bowel movements (BMs) per day for a week or more. The study design included a one-week run-in period followed by one week of CASAD ± a two-week optional continuation period. The primary endpoint was efficacy of one week of CASAD treatment in decreasing the number of BMs per day by ≥20% when compared with the baseline run-in period. Secondary objectives included tolerability and safety and the impact on QOL using the MD Anderson Symptom Inventory-Thyroid questionnaire (MDASI-THY).

Results: Ten MTC patients (median age = 52 years, 70% female, 80% white) were enrolled. All had distant metastases, and median calcitonin was 5088 ng/mL (range 1817-42,007 ng/mL). Ninety percent had received prior antidiarrheals, and 40% of these had used two or more drugs, including tincture of opium (30%), loperamide (50%), diphenoxylate/atropine (20%), colestipol (10%), or cholestyramine (10%). Of seven evaluable patients, four (56%) had ≥20% reduction in BMs per day. Six out of seven patients discontinued their prior antidiarrheals. Best response ranged from 7% to 99% reduction in mean BMs/day from baseline. Five out of seven patients considered CASAD a success, and they opted for the two-week continuation period. Improvements in diarrhea and all six interference items assessed by MDASI-THY were noted at weeks 1 and 3. Total interference score was significantly improved at three weeks compared with baseline (p = 0.05). An oral levothyroxine absorption test was performed in one patient; malabsorption of levothyroxine was not observed. Adverse events included flatulence (40%), bloating (10%), heartburn (10%), and constipation (10%).

Conclusions: CASAD is a promising strategy for treatment of MTC-related diarrhea. In this small pilot study, improvements in frequency and quality of diarrhea as well as QOL were noted. Further studies in this population are warranted.

FIG. 1.

Study scheme. Evaluations were performed before the study drug was started (at the end of the one-week run-in period), and at 3 ± 1 days and 7 ± 2 days after the drug was started. Patients who choose the option of receiving the study drug for an additional two weeks were evaluated at the end of three weeks as well.

FIG. 2.

Efficacy of calcium aluminosilicate antidiarrheal (CASAD) at day 7 (primary endpoint) compared with the baseline run-in period in evaluable patients (n = 7). Light gray bars represent the mean number of BMs per day during the run-in period. Dark gray bars represent the mean number of BMs per day during the one-week treatment with CASAD. Four out of seven patients met the primary endpoint (gray arrows). *Patient 7 continued all three antidiarrheal meds during the run-in period but stopped them during the week of CASAD treatment.

FIG. 3.

Best response of CASAD in evaluable patients (n = 7) during the entire study period. The quantity of stools is represented at two time points and reported as percent decrease in the mean number of BMs per day compared with the baseline. All patients had a decrease in number of BMs per day ranging from 7% to 99% over a 3–21 day period. The quality of stools is depicted in colors (watery = light gray, semisolid = dark gray, and solid = black).

FIG. 4.

Diarrhea (A) and quality of life assessment (B) using MDASI-THY questionnaire. (A) The MDASI-THY diarrhea score improved at day 7 and week 3 compared with the baseline run-in period. (B) Improvement in all MDASI-THY interference items (general activity, mood, work, relationships with others, walking, and enjoyment of life).