Individualized Study of Refeeding to Optimize iNpatient Gains (i-STRONG)

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Atypical Anorexia Nervosa
• Intervention / Treatment: Other: Individualized Caloric Refeeding (ICR); Other: Higher Calorie Refeeding (HCR)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University Lucille Packard Children's Hospital
    • San Francisco, California, United States, 94158
      • University of California, San Francisco Benioff Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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:

  1. night time heart rate (HR) <45 bpm,
  2. systolic blood pressure (SBP) <90 mmHg,
  3. temperature <35.6° C,
  4. orthostatic Δ HR >35 bpm, or
  5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage median BMI (mBMI) Over 12 Months	Measured BMI will be divided by the mBMI for age and sex per national growth data to give the percentage mBMI.	12 months post-study hospitalization
Eating Disorder Examination Questionnaire (EDE-Q) Score Over 12 Months	The EDE-Q will be self-administered; scores range from 1 to 6, with higher scores indicating greater severity and a worse outcome.	12 months post-study hospitalization

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Stanford University
• Investigators: Principal Investigator: Andrea K Garber, RD, PhD, University of California, San Francisco; Principal Investigator: Neville H Golden, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2021
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): April 14, 2026

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 19, 2021

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Malnutrition; Refeeding; Adolescent Medicine; Nutritional Rehabilitation
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Anorexia; Anorexia Nervosa
• Other Study ID Numbers: 2R01HD082166-06A1 (U.S. NIH Grant/Contract); 20-32551 (Other Identifier: UCSF IRB); R01HD082166 (U.S. NIH Grant/Contract); HD082166 (Other Identifier: Federal Identifier, per NIH application); P0547076 (Other Identifier: NIH Application Identifier)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No