Individualized Study of Refeeding to Optimize iNpatient Gains

Study Overview
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Brief Summary
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The primary purpose of the trial is to compare the efficacy and safety of Individualized Caloric Refeeding (ICR) to the new standard of care, Higher Calorie Refeeding (HCR), in hospitalized patients with atypical anorexia nervosa (AAN), and clinical remission over one year of follow-up.

Detailed Description
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Atypical Anorexia Nervosa (AAN) is a new diagnosis describing patients with malnutrition and significant weight loss yet normal weight. These patients responded poorly to HCR, the superior refeeding treatment in the parent trial, which was designed for low-weight patients with typical AN. The proposed trial will examine the safety and efficacy of a new treatment for AAN with the potential to improve treatment outcomes for this diverse and growing patient population. The major finding motivating the proposed trial is that participants with AAN gained weight 40 percent slower and required 3.0 additional days in hospital to restore medical stability on HCR, as compared to AN. The research team has developed Individualized Caloric Refeeding (ICR), which doses calories to weight consistent with other pediatric treatments (e.g. medication). The primary purpose of the proposed trial is to compare the efficacy and safety of ICR to the new standard of care (HCR) in hospitalized patients with AAN. The investigators hypothesize that ICR will restore medical stability faster than HCR with no increase in electrolyte abnormalities. After hospitalization, the major barrier to care in AAN is lack of consensus on clinical remission and whether these formerly overweight patients should gain weight to recover. The research team will examine metabolic, hormonal and psychological markers during long-term follow-up, toward the goal of developing a definition of clinical remission in AAN. Design Summary: Randomized controlled trial in N=74 participants age 12-24 with AAN, consented upon hospital admission, randomly assigned to ICR or HCR, followed daily in hospital and at 3, 6, 9 and 12 mo.

Official Title
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Renewal of the Multi-center Randomized Controlled Trial of Refeeding in Anorexia Nervosa

Conditions
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Atypical Anorexia Nervosa

Intervention / Treatment
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* Other: Individualized Caloric Refeeding (ICR)
* Other: Higher Calorie Refeeding (HCR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 12-24 yrs Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for AAN Hospitalized with medical instability, as defined by: night time heart rate (HR) <45 bpm, systolic blood pressure (SBP) <90 mmHg, temperature <35.6° C, orthostatic Δ HR >35 bpm, or orthostatic Δ SBP >20 mmHg Exclusion Criteria: Bulimia nervosa Current pregnancy Chronic disease (e.g. immune, renal disease) Acute/active suicidality or psychosis Hospital admissions for refeeding in the prior 6 mo.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be recruited upon hospital admission at the University of California, San Francisco (UCSF) and Stanford and randomly assigned to Individualized Caloric Refeeding (ICR) or Higher Calorie Refeeding (HCR) for the duration of the hospitalization. Treatment ends at hospital discharge with open follow-up for one year. Participants followed daily in hospital and at 3mo, 6mo, 9mo, and 12mo post-discharge.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individualized Caloric Refeeding (ICR)<br>Starting 50 kcal/kg/d, increasing by 200 kcal/d to goal | Other: Individualized Caloric Refeeding (ICR)<br>* Meal-based refeeding in hospital, starting at 50 calories per kilogram of body weight, and increasing by 200 calories per day until caloric goal achieved<br>* Other names: ICR;|
| Active Comparator: Higher Calorie Refeeding (HCR)<br>Starting 2000 kcal/d, increasing by 200 kcal/d to goal | Other: Higher Calorie Refeeding (HCR)<br>* Meal-based refeeding in hospital, starting at 2000 calories per day, and increasing by 200 calories per day until caloric goal achieved<br>* Other names: HCR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Achieve Medical Stability in Hospital | Medical stability will be adjudicated by a five-point index: (1) 24 hour heart rate of 45 beats/min or more, (2) systolic blood pressure of 90 millimeters of mercury (mmHg) or more, (3) temperature of 35.6° C or more, (4) orthostatic increase in heart rate of 35 beats/min or less, (5) orthostatic change in systolic blood pressure of 20 mmHg or less. | Inpatient hospitalization from day of admission to day of discharge, average 1-2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of low serum electrolytes during refeeding in hospital | Incidence of low electrolytes will be defined as: (1) hypophosphatemia less than 3 milligrams per deciliter (mg/dL), (2) hypomagnesaemia less than 1.8 mg/dL, and (3) hypokalemia less than 3.5 milliequivalent per liter (mEq/L) during hospitalization. | Inpatient hospitalization from day of admission to day of discharge, average 1-2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malnutrition, Refeeding, Nutritional Rehabilitation, Adolescent Medicine