Feeding Behaviors Clinical Trial
Official title:
Effects of Cyproheptadine on Growth and Behavior in Pediatric Feeding Disorders
The purpose of this study is to examine the effect of standard dosing of cyproheptadine for both cycled and continuous administration, as compared to no medication, on appetite stimulation and growth in the pediatric gastroenterology feeding team patient population. The secondary aim is to evaluate the effect, if any, of the suspected tachyphylaxis that is commonly associated with cyproheptadine use. The third aim will be to examine the type and duration of side effects of cyproheptadine in this population. The ultimate goal will be to create a standardized protocol for cyproheptadine therapy in children with feeding disorders and suboptimal growth.
BACKGROUND, SIGNIFICANCE, AND RATIONALE Failure to thrive or inadequate weight gain is a
frequent complaint amongst patients seen by general pediatricians and pediatric
gastroenterologists. The reasons behind this diagnosis vary widely including, but not limited
to feeding disorders of diverse etiologies, poor environmental structure and inadequate
intake, medication side effects, swallowing disorders, and a variety of underlying organic
diseases. For most feeding disorders, behavioral feeding techniques and strategies to
increase caloric intake is utilized to correct the suboptimal growth. However, feeding
disorders are sometimes so imprinted that behavioral interventions may be insufficient to
promote ideal growth or, if sufficient for growth, are inadequate in helping children avoid
or graduate from nutritional support such as enteral tubes. For this reason, medications that
promote and stimulate appetite and weight gain are frequently used in children with feeding
disorders.
In pediatric gastroenterology practice, cyproheptadine is the most commonly used drug for
appetite stimulation, weight gain, and feeding intolerance in younger children with feeding
disorders. A first generation histamine and serotonin antagonist, cyproheptadine is thought
to promote appetite stimulation and weight gain by increasing insulin-like growth factor-1
(IGF-1) concentration. It may also interact with receptors in the ventromedial hypothalamus
and exert hormonal effects. While the exact mechanism of action is still being investigated,
several studies have evaluated the benefits of cyproheptadine in select patient groups,
including patients with cystic fibrosis, cancer, undernourished children, and children with
feeding disorders. These studies have all reported that cyproheptadine promotes weight gain
and stimulates appetite. Reported side effects of cyproheptadine in these studies are
primarily related to drowsiness which tends to significantly improve or resolve within two
weeks of use. Another undesired effect is the development of drug tolerance, i.e.
tachyphylaxis. To avoid this, it is common clinical practice to cycle on and off the
medication a few weeks each month.
While a few studies report outcomes of the use of cyproheptadine in children with feeding
disorders or failure to thrive, these studies have enrolled only small patient cohorts and
there are no randomized trials in children enrolled in a feeding team program. Two recent
studies examined the role of cyproheptadine in patients who are undernourished or followed in
pediatric feeding programs. However, a randomized study examining the effects of continuous
cyproheptadine versus a fixed cycled medication dosing versus abstaining from medication has
not been performed in the pediatric gastroenterology population.
OUTCOME MEASURES:
Number of Participants in Study: The total number of patients required for this study is 75
(25 in each group). The groups consist of three treatment arms:
1. continuous use of cyproheptadine
2. cycled cyproheptadine or
3. no drug intervention
This number was derived from looking at past statistical data from other studies and using
similar power, alpha error, and beta error. Investigators used Analysis of Variance (ANOVA)
analysis for multiple groups looking at repeat measures within factors. Alpha error was 0.05,
Power 0.95.
Data Collection: The following categories of data will be collected (see subsections list
below): medical record number (MRN), demographics, feeding behavior, side effects experience
from use cyproheptadine, 24 hour diet recalls, medical history, and anthropometrics.
Demographic Information: Data will be collected as part of the demographics questionnaire.
This includes participant's age, sex, ethnicity, identification of primary caretaker,
caretaker's relation to participant, caretaker education level, and caretaker marital status.
Feeding Behavior Questionnaire: Patients/parents will complete the Mealtime Behavior
Questionnaire (MBQ). Participants' guardians will complete the Mealtime Behavior
Questionnaire (MBQ). This is a validated, 31-item, parent-report questionnaire assessing the
mealtime behavior structure in young children above 2 years.
The questionnaire measures variables including:
1. food refusals/avoidance
2. food manipulation
3. mealtime aggression and
4. choking/gagging/vomiting related to meals.
Each behavior is assigned a frequency scale with 1 corresponding to "never" and 5
corresponding to "always." The MBQ then consist of a total score and four subcategory scores
(listed above).
24 Hour Diet Recall: Guardians of participants will be questioned weekly regarding oral
intake (type of food consumed and amount) over the past 24 hrs. Caloric intake will be
calculated based on these recalls and compared across duration of study.
Cyproheptadine Side Effect Questionnaire: Guardians will undergo weekly questionnaire looking
at common side effects of cyproheptadine. A list of side effects will be read to the
participant's guardians with positive (yes) or negative (no) replies if the participant has
experienced individual side effects since the last survey.
Medical Information: Data collected will include anthropometrics at initial and final visit
(weight, height, BMI, mid-arm circumference, upper arm skin fold), current and past medical
diagnoses and surgeries, current medications, current gastrointestinal symptoms, dependence
on tube feeds
RISK CATEGORY:
Research not involving greater than minimal risk to the children.
KNOWN SIDE EFFECTS OF CYPROHEPTADINE:
Cyproheptadine has both antihistamine and antiserotonergic and has side effects related to
these mechanisms. These side effects include drowsiness or sleepiness, confusion, excitement,
fatigue, insomnia, hallucinations, blurred vision, tinnitus, dizziness, tachycardia, increase
perspiration, appetite stimulation, weight gain, constipation, diarrhea, changes in frequency
of urination, thickening of secretions, and dry mucus membranes. Over-dosage can results in
atropine-like effects as well as central nervous depression, convulsions.
SECURITY OF DATA COLLECTED:
All investigators have received Health Insurance Portability and Accountability Act (HIPAA)
training and a certificate of completion for the Collaborative Institutional Training
Initiative (CITI) training course on the protection of human research subjects before
starting the review. Information derived from questionnaires, data collection will be
compiled on one central data collection form. These forms will be coded (have a special
identifier number that is linked to patient's MRN). The central database used for data
collection will be password protected. A separate secure (password protected) database will
link the coding number to the patient's MRN. Only the principal investigator (PI),
co-investigators and the members of the study team will be gathering the data and have access
to the study database. Paper records will be locked in file cabinets within the
Gastroenterology office area and electronic records will be stored in password-protected
computers. Each subject's identifying number and related electronic data will be kept on a
secured, password-protected database that provides access only to the PI and research staff.
Only authorized research personnel will have access to the databases and paper records.
PROVISION FOR THE PROTECTION OF PRIVACY OF SUBJECTS (confidentiality, health and financial
risks) AND TO MAINTAIN THE CONFIDENTIALITY OF DATA:
Data will be stored on Medical College of Wisconsin secured shared drives.
PROVISIONS FOR MONITORING DATA TO ENSURE THE SAFETY OF SUBJECTS; AND ADDITIONAL SAFEGUARDS TO
PROTECT THE RIGHTS AND WELFARE OF SUBJECTS WHO ARE LIKELY TO BE VULNERABLE:
The PI will monitor the health of all patients in the study per standard clinical practice.
Primary and Co-investigators will monitor protocol adherence and supervise data collection,
entry, and analysis.
ANTICIPATED BENEFITS ASSOCIATED WITH THE PROTOCOL (value or desired outcome / advantage) TO
HUMAN RESEARCH PARTICIPANTS AND SOCIETY (medical, psychosocial, altruistic) Anticipated
direct benefits of this study include the improvement in appetite/behavior and growth amongst
the patients receiving cyproheptadine. These benefits may also be present in group abstaining
from cyproheptadine due to standard education that is given to all groups. However, the
investigators anticipate these benefits to be significantly lower in this group as compared
to patients who are on cyproheptadine. Long-term benefits include the creation and
utilization of a protocol outlining the use of cyproheptadine in feeding team patients. The
results of this study will also address the side effect profile of cyproheptadine in this
population. It may also further investigators' knowledge of the treatment approaches that are
most successful, allowing physicians to develop standardized care to better serve these
patients and their families.
STOPPING POINTS THAT WOULD NOT ALLOW THE STUDY TO CONTINUE AS PROPOSED:
Stopping points for the study include achieving adequate information on enough of the goal
subjects, inability to obtain enough data, or patients/caregivers electing to discontinue the
study.
DESCRIBE HOW THE CONSENT (AND ASSENT, IF APPLICABLE) PROCESS WILL TAKE PLACE. INCLUDE A LIST
OF APPROPRIATELY TRAINED PERSONNEL WHO WILL BE INVOLVED.
Written informed consent for participation will be obtained from guardians for their child's
participation. Consent will be obtained by study personnel at the participant's appointment
in the GI Clinic. Participants' consent will allow for accessing information collected for
program evaluation/clinical purposes. Participants' guardians will have the option of having
the consent document read aloud to them to facilitate understanding. Copies of signed consent
documents will be given to participants' guardians. Consent will be obtained by the study's
principal investigator, co-investigators, or members of the research team. As additional
research staff or team members are added, their names will be submitted to the International
Review Board (IRB) as a protocol amendment to allow them to obtain consent.
PROCEDURES TO BE EMPLOYED IN ANALYZING DATA (including a power analysis) AND THE ANTICIPATED
SIGNIFICANCE OF THE PROPOSED STUDY Analyses will be conducted with Statistical Package for
the Social Sciences (SPSS) and Statistical Analysis System (SAS) software programs.
Probability levels of < .05 will be used as cut offs for statistical significance.
Descriptive analyses will examine distribution normality and the extent to which parametric
test assumptions are met. Descriptive analyses will also provide summary information about
participant characteristics. Pearson correlations will be used to examine relationships
between continuous variables, while chi square analyses will examine associations between
categorical variables.
The key significance of this study is the analysis of the effect that cyproheptadine has on
stimulating weight gain and improving behaviors associated with feeding. In addition, it will
help give clear comparison between the use of continuous versus cycled cyproheptadine.
Cyproheptadine has been suspected to have tachyphylaxis after a couple weeks and many
practitioners implement cycling of medication without clear evidence supporting this
practice. Investigators expect after this study to be able to design a protocol regarding use
of cyproheptadine in feeding team patients.
FINANCIAL RELATIONSHIPS:
There are no financial relationships or interests to disclose.
ADVERTISEMENTS / FLIERS (how will they be used / distributed):
None will be used
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