New Study Published On Oxytocin Treatment In Children With PWS

new-study-published-on-oxytocin-treatment-in-children-with-pws.jpgA new study examining the effects of oxytocin (OT) in children with PWS has been published by Dr. Anita Hokken-Koelega and colleagues at the Dutch Growth Research Foundation (Promising effects of oxytocin on social and food-related behaviour in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial). This study examined the effects ofoxytocin on social behavior, food behavior, food intake, satiety and weight, in children age 6-14. The study used a ‘randomized, double blind, placebo controlled, crossover’ design. 

This is a rigorous study design in which there is a period where the patient receives drug and a period where they receive placebo, but neither patient/family, nor doctor knows which is being used when, until the study is ‘unblinded’ and the results analyzed. In this case, participants received either oxytocin or placebo for 4 weeks, then were switched to the other for 4 weeks. A number of questionnaires were administered at the end of each period to assess changes in social behavior, food related behavior, food seeking, satiety and hyperphagia. Additional measures (weight, BMI, % fat, food intake and rate) were also performed at the end of each 4 week period.

The study included 25 children with PWS, age 6-14 years. The dose was determined based on the size of the child, and ranged from a low of 24 to a high of 48 IU of OT administered per day.  

No adverse events (safety problems) were found during the entire study period, which is encouraging. In looking at the results for the entire group of 25 children, oxytocin did not produce any significant change in any measure of social behavior (measured by a new “Oxytocin Study Questionnaire”, developed by the researchers), food related behaviors, food intake or satiety (measured by the Oxytocin Study Questionnaire, the Dykens hyperphagia questionnaire, and by measuring the amount of food and rate of food eaten at a standardized breakfast). Weight, BMI, and % fat were also unchanged in OT vs. placebo.

This finding was disappointing, but the researchers were interested in seeing how age of the participant might influence the results – and when they looked at the results broken down by age groups, some differences were seen. The authors performed a “subgroup analysis”, looking at the results from older (8 individuals, age 11-14) and younger participants (17 individuals, age 6-10.99) separately. This kind of analysis can suggest a particular subset of individuals in a population who might have better outcomes from the treatment being studied. Care must be taken, however, in doing a subgroup analysis such as this, so as not to over-interpret the data. (see Hirji, 2009)

In looking at the younger children only (<11 year old, 17 individuals), features such as ‘anger’, ‘sadness’ and ‘conflict’ improved significantly when the children were being treated with OT compared to placebo. Overall, 10 of the 17 parents reported improvements in social behavior while the child was on oxytocin, compared to 5 of 17 reporting improvements during the placebo phase. Notably, none of the caregivers of the younger group reported worsening of any of the social measures while receiving oxytocin. Measures of ‘happiness’, ‘social interaction’ and ‘disruptive behavior’ were not significantly changed between treatment and placebo in this age group, nor were there significant changes in eating behavior, rate of eating, amount eaten or weight and BMI during the treatment period compared to placebo. However, one questionnaire about food behavior (food-related behavior questionnaire) showed significantly more reports of improvement (7 of 17) compared to worsening (0 of 17) in children receiving oxytocin (with 10 of 17 caregivers reporting no change). Overall, the authors conclude that intranasal OT administration is a promising treatment for young children with PWS.

The results were not as promising in the older children. None of the families reported improvements in social behavior during oxytocin treatment: most reported no change, but where there was a change, it was for the worse in certain measures (happiness, anger, sadness). Other measures (food related behaviors, food seeking, hyperphagia, weight, satiety) were not significantly different in OT vs. placebo. So, overall, no benefit was seen with OT therapy.

The reason for lack of benefit in older children is unclear, and it’s important to note that it was a very small sample size (n=8), so additional work will need to be done before anything can be concluded. Keeping these caveats in mind, the authors do speculate, however, that there may be an age related effect resulting in a decline in the oxytocin system as children reach puberty; a possibility that should be further investigated. It’s possible that manipulating the treatment (for example, extending the treatment period, modifying the dosing) could improve effectiveness in this group, and this will be for additional studies to determine.

The authors also looked for correlations of efficacy with other features (genetic subtype, sex, BMI, etc), but none were detected. They also studied the level of oxytocin in the blood prior to receiving any therapy, and they found a wide range of oxytocin levels between children, with no definitive association between baseline OT levels and effects during treatment.

Altogether, this study adds to our growing knowledge of OT in PWS, but it is also a reminder that we currently face significant limitations in understanding how best to use OT in PWS. For example, are the beneficial effects really confined to younger children, or does negative finding on older children just reflect a small sample size, or dosing and duration that isn’t appropriate? In addition, although there was overall benefit in the younger children, the response was still quite variable. Parents whose children responded positively to OT therapy were enthusiastic about the improvement and felt it had a big impact, but a little less than half of the families reported no improvement.

What separates those seeing benefit from those who don’t? Are there genetic reasons: baseline OT levels, OT receptor variants (which are known to influence responsiveness in the normal population) and expression differences, differences in overall hormone processing that is unique to PWS? How do metabolic or environmental factors impact OT response: are there certain medications that improve or interfere with beneficial effects, behavioral methods strengthen or work against the biological effects of OT? Are the dosing amounts and intervals optimal? Dosing is challenging with OT, and it's possible that administering too much OT will negate a positive effect or cause a negative emotional response in PWS. Are the assessments of changes in social interaction and food behavior used in this study and others adequately capturing the changes so that they “show up” in rigorous statistical analyses?

For example, measuring changes in food related behavior in younger children is challenging given that most children in the 6-10 age group often do not exhibit food-seeking behaviors –so seeing changes using questionnaires can be difficult. To that end, some quantifiable measures are currently in development and may prove useful. Looking ahead, it’s clear that additional, validated measures to capture social and food behavior changes across age groups is a priority, as is the ability to accurately quantify the level of OT (active form) in the blood.

In conclusion, this study brings up some interesting ideas that will need to be confirmed using well-powered clinical studies specifically designed to examine the effect of age on oxytocin treatment outcomes. In addition, this study illustrates the importance of continued investigation into OT for PWS, and reinforces that it’s best for individuals with PWS to receive OT only in the context of clinical trials. In that setting, the quality and consistency of OT is well regulated, potential safety issues can be fully monitored, and the effects can be measured in such a way that we can advance the understanding of this potential therapy to effectively treat individuals with PWS.

The study was supported by research grants of Dutch Prader-Willi Fund and of Dutch Growth Research Foundation (Prader-Willi Fonds and Kind en Groei).

For updated information on PWS clinical trial opportunities and to sign up for a monthly PWS Clinical Trial Alert, visit the PWS Clinical Trials page.PWS Clinical Trials

Topics: Research

Theresa Strong


Theresa V. Strong, Ph.D., received a B.S. from Rutgers University and a Ph.D. in Medical Genetics from the University of Alabama at Birmingham (UAB). After postdoctoral studies with Dr. Francis Collins at the University of Michigan, she joined the UAB faculty, leading a research lab focused on gene therapy for cancer and directing UAB’s Vector Production Facility. Theresa is one of the founding members of FPWR and has directed FPWR’s grant program since its inception. In 2016, she transitioned to a full-time position as Director of Research Programs at FPWR. She remains an Adjunct Professor in the Department of Genetics at UAB. She and her husband Jim have four children, including a son with PWS.

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