I found out about this study through the Craniopharygioma mailing list, but haven't seen it on this site so I thought I would post. I am posting this letter which was sent to all members of the cranio mailing list. I am sure the doctor doing the study won't mind, this way the word gets to more people. I hope some of you will find this useful:

To Parents and Patients in the Craniopharyngioma Support Group: A recent study conducted by our group at St. Jude Children's Research Hospital has recently been featured in the lay press, and I would like to take this opportunity to explain our findings, and its possible implication for the welfare of brain tumor patients in general. As you are probably aware, one of the serious sequelae of brain tumors or leukemia and their treatment is rapid and intractible weight gain. The weight gain occurs even on a normal calorie diet, and even severe caloric restriction does not result in weight loss. Patients affected with this syndrome become massively overweight over the course of several years. These patients also feel bad, with malaise, fatigue, sleepiness, and lack of exercise. This syndrome is called "hypothalamic obesity", because destruction of the ventromedial hypothalamus (VMH) in rats causes the same syndrome. This is where the concept of the "satiety center" in the brain came from. Unfortunately, there is no cure, and until recently, there was no treatment for this disorder. Indeed, physicians did not even understand the nature of the signals that caused the weight gain. Some thought it was due to endocrine problems like growth hormone deficiency or hypothyroidism, but giving these hormones to patients with hypothalamic obesity did not alter the weight gain. However, in 1975, Dr. George Bray and colleagues at UCLA discovered that if you cut the vagus nerve of the VMH-lesioned rat (an important nerve that leads from the brain to the pancreas), the weight gain did not occur. They went on to show that the nerve cut prevented an abnormal increase in the rise of the hormone insulin, the body's major energy-storing hormone. They postulated that the brain damage led to abnormal vagus nerve firing, which in turn led to excessive insulin secretion, which shunted all the energy that the animal ate away from the brain, liver, kidneys and muscles, and put it into fat. Despite these important animal studies, a similar phenomenon was never shown in humans, and the hypothesis remained unproven. At St. Jude, we have numerous patients with hypothalamic obesity. As a pediatric endocrinologist, I was faced with the task of assisting them. Two years ago, we started a study in these patients to try to prove Dr. Bray's hypothesis. We treated eight patients with a drug called octreotide, which is a long-acting analog of the hormone somatostatin. Somatostatin is found throughout the body. Its main function is to block growth hormone secretion from the pituitary gland (its main use is in acromegaly, an adult condition of growth hormone excess). However, in the pancreas, it blocks insulin secretion. So this seemed like an excellent candidate to see if blocking insulin secretion could reduce weight gain, or even induce weight loss in these patients. Eight patients entered the study. They were gaining weight at the rate of 2.2 lbs/month. Their average Body Mass Index (a measure of obesity taking into account height) was 36 (Normal below 25). Before starting the octreotide, we performed oral glucose tolerance tests on each patient. We found that they oversecreted insulin-a normal peak response is about 100, our patients mean peak response was 265. We also noted that they secreted insulin for a much longer time. Normally the peak is reached in 30 minutes, and the levels are back down at 3 hours. In our patients, the peak was at 120 minutes, and the levels were not back down until 5 hours. This means they were releasing more insulin, and for a longer time. The patients were kept on the medicine for 6 months. The mean weight loss over the 6 months was 1.7 lbs/month. 5 patients lost, 2 stabilized, and 1 patient gained weight. Our best responder lost 28 lbs, and our worst responder gained only 4 lbs. Their average caloric intake decreased by an average of 700 calories/day. We tested their insulin responses again. Now their mean response was 114, and they reached their peak in 30-60 minutes, clearly much improved. The other feature of the treatment was that 7/8 patients said that they felt much better; more active, less sleepy, easier to concentrate in school. One patient started competitive swimming, two started lifting weights, and one became the manager of his high school baseball team. Two patients stayed on the medicine for a full year. One lost 48 lbs, one lost 36 lbs. The only signficant complication was that 4/8 patients developed gallbladder sludging or numerous small gallstones (a known side-effect of octreotide). Clearly, these patients appear to have been helped by this therapy. However, octreotide MUST be given by injection. Our patients had to take 3 injections a day. That's similar to the way diabetes is treated. This means that taking octreotide is a MAJOR commitment on the part of the parents and child. In addition, there were a number of problems with the study. 1) Only eight patients. 2) No control group. 3) Not placebo-controlled. 4) We don't even know if the dose was right, as octreotide is not a "kid's" medicine. For this reason, we will be embarking on another study, to be conducted here at St. Jude. This study will probably start 3-4 months from now. This study will recruit 20 patients with hypothalamic obesity due to brain tumors or leukemia, ages 4 to 21 years. This study will last 1 year. It will be conducted as a double-blind, placebo-controlled crossover trial. That means, there will be 6 months of octreotide (3 shots per day) and 6 months of placebo (salt water, 3 shots per day). It could go octreotide-placebo, or placebo-octreotide; neither you nor the doctors will know. However, we will be opening this study to other centers. If you and your pediatric endocrinologist at home are interested in this study, funds will be available to fly you and your child to Memphis 3 times; once at the beginning, once at the changeover (6 months), and once at the end of the study (12 months). The hospitalization each time will last two days. All transportation, hospitalization, laboratory, and drug costs will be provided free of charge. Your pediatric endocrinologist MUST consent to your child's being in the study, because they will have to see your child once a month during the study to monitor height, weight, draw lab tests, and send us the results. As you can see, this new study is not simple. But we have found from our previous eight patients that the benefit clearly outweighs the cost and the inconvenience.

If you, your child, or your pediatric endocrinologist would like more information, please contact me at 901-572-3292, or E-mail me at rlustig@utmem1.utmem.edu. If your child would like to be considered for this study, we will first need a letter from your pediatric endocrinologist giving the pertinent past history, a growth curve, and a letter of commitment to see the patient at 1,2,3,4,5,7,8,9,10, and 11 months. Best wishes for your child's health.

Sincerely,

Robert Lustig, M.D. Associate Professor Division of Pediatric Endocrinology and Metabolism University of Tennessee, Memphis 50 North Dunlap Memphis, TN 38103