Diarrhea occurs in approximately 50% of people with AIDS at some point during their illness. A specific cause, such as an opportunistic infection, is not always found. Initial non-randomized studies had found that octreotide (Sandostatin) injections could improve diarrheal symptoms among those with AIDS-associated refractory, chronic diarrhea. For example, about 25% of people with cryptosporidial diarrhea respond to octreotide injections leading to one-third the daily quantity of diarrhea and half the number of daily episodes.
A recently published controlled trial found no or borderline statistically significant differences in diarrheal measurements when comparing octreotide (OCT) to placebo (PBO) among people with AIDS and refractory diarrhea. D.M. Simon, MD, and colleagues from the Albert Einstein College of Medicine reported their findings in the June 1995 issue of the journal Gastroenterology. One of the co-authors is John Cello, MD, from UCSF San Francisco General Hospital. Octreotide is a synthetic peptide hormone.
During a 3-week trial, 129 people with AIDS with a refractory diarrheal stool weight of greater than 500 grams per day were randomized to receive either OCT or PBO. The OCT dose was increased 100 micrograms every 8 hours based on weekly 72-hour stool collections. After the 3 weeks, participants received open-label OCT at a maximum dose of 500 micrograms every 8 hours. A stool weight that decreased by 30% was defined as a response.
After 3 weeks, 48% of OCT-treated and 39% of PBO participants responded. At a dose of 300 micrograms every 8 hours, 50% of OCT and 30% of PBO participants responded (this was not statistically significant). For those with a baseline stool weight of 1,000-2,000 grams a day, 57% of OCT and 25% of PBO participants responded (this approached statistical significance). There were no differences between responders and non-responders when analyzing by CD4 count, duration of diarrhea, body weight, and presence or absence of infectious diarrheal organisms. The authors acknowledge that a relative lack of response may be due to a small sample size, octreotide dosage and/or trial duration.
In an accompanying editorial by Donald Kotler, MD, of St. Lukes-Roosevelt Medical Center in New York, limitations of the study were noted. Dr. Kotler indicated that the study was not well controlled for the effects of food intake, pancreas function or assurance of compliance in treatment and stool collection. Dr. Kotler states that octreotide is likely to be most effective in treating a subgroup of people with AIDS with diarrhea that is associated with abnormal secretion of fluids in the small intestine.
Kotler DP. Octreotide therapy for human immunodeficiency virus-associated diarrhea: pitfalls in drug development. Gastroenterology 108(6): 1939-1941. June 1995.
Simon DM and others. Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea. Gastroenterology 108(6): 1753-1760. June 1995.