Refeeding Syndrome in Anorexia Nervosa

Anorexia Nervosa Clinical Trial

Official title:

Multi Site Randomized Controlled Trial on Refeeding Syndrome in Anorexia Nervosa

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02621229
• Other study ID #: IRB-33865
• Status: Recruiting
• Phase: N/A
• First received: November 17, 2015
• Last updated: October 13, 2016
• Start date: December 2015

Study information

• Verified date: October 2016
• Source: Stanford University
• Contact: Kristina Saffran
• Phone: 917-513-0056
• Email: ksaffran[@]stanford.edu
• Is FDA regulated: No
• Health authority: United States: Data and Safety Monitoring BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this multi-center randomized controlled trial is to compare lower calorie refeeding to higher calorie refeeding for hospitalized adolescents and young adults with AN. The investigators will compare efficacy (achievement and maintenance of clinical remission at 12 months), safety during hospitalization, and cost effectiveness (including costs of initial and re hospitalization, 12 month follow up and safety/adverse events).

Description:

Anorexia nervosa (AN) is an illness commonly diagnosed in adolescence with low recovery rates and high healthcare costs. The major medical complication of AN is malnutrition. Caloric restriction, purging and other weight control behaviors can lead to medical instability (abnormal vital signs) requiring hospitalization. The primary goal of hospitalization is to restore medical stability by reintroducing nutrition, or "refeeding". Within 12 mo of discharge, 43% of patients will require medical rehospitalization. This results in a costly course of recovery, given that eating disorders are the most expensive among primary mental health diagnoses requiring hospitalization. Several lines of inquiry seeking to identify characteristics or short-term outcomes that may predict better recovery in AN point to rapid short-term weight gain as a strong predictor of long-term outcomes. Greater weight gain in hospital predicts weight recovery at 12 moand, in psychotherapeutic trials, greater weight gain during the first 3-4 wk (1.7-1.9 lb/wk) predicts full remission at 12 mo. Unfortunately, the currently recommended approach, Lower Calorie Refeeding (LCR), is associated with slow weight gain and prolonged hospital stay. Treatment is now moving sporadically toward Higher Calorie Refeeding (HCR) in the hope of improved recovery. However, no study to date has directly compared these two approaches.] Since the refeeding syndrome, characterized by rapid electrolyte shifts, delirium and cardiac arrest in response to the influx of nutrients was first described around WWII, refeeding has been approached with caution. Following documentation of this syndrome in patients with AN, conservative, consensus-based recommendations for LCR were developed to ensure safety. LCR typically begins around 1200 kilocalories (kcal) per day and advances by 200 kcal every other day. The investigators found that patients initially lose weight on this "start low and go slow" approach and require prolonged hospitalizations to achieve medical stability. This finding contributed to recognition of the "underfeeding syndrome". In subsequent studies, the investigators demonstrated that HCR produced faster weight gain and shorter hospitalization. While no increased risk of refeeding syndrome has been reported using HCR, the variety of electrolyte supplementation protocols being used to manage risk have not been examined.

Findings from these observational and retrospective studies have been rapidly accepted by many clinicians and insurers and HCR is now being integrated into practice in many hospitals. However, there are major gaps in the evidence necessary to adopt HCR as the new standard of care. These gaps are: 1.) It is not known if HCR impacts clinical remission, which is typically defined as the combination of weight and cognitive recovery at 12 mo. 2.) The safety of HCR has not been confirmed. The hallmark electrolyte imbalances of refeeding syndrome occur frequently and still have not been systematically examined on differing refeeding protocols. 3.) The relative cost-effectiveness of the two approaches has not been established.

The investigators propose to conduct a randomized controlled trial (RCT) at two sites to directly compare HCR and LCR for refeeding in AN. To accomplish the following aims, 120 adolescents will be enrolled upon admission to hospital for malnutrition secondary to AN and randomized 1:1 to HCR (beginning with 2000 kcal and advanced 200 kcal/d) or LCR (beginning at 1400 kcal/d and advanced 200 kcal every other day) until medical stability is restored. Participants will be followed for 12 mo after randomization: Daily while in hospital and at follow-up [10 dy],1 mo, 3 mo, 6 mo, and 12 mo after randomization.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 24 Years

Eligibility

Inclusion Criteria:

• Adolescents hospitalized for medical instability secondary to malnutrition will be eligible as follows.

Inclusion criteria:

1. diagnosis of AN, atypical AN

2. age 12-24 years

3. no hospital admissions for the previous six months

4. meet hospitalization criteria (daytime HR < 50 bpm or night time HR < 45 bpm, BP <90/45 mmHg, temperature < 36? C or orthostasis defined by increase in HR > 20 bpm or decrease in systolic BP > 20 mmHg or decrease in diastolic BP > 10 mmHg from lying to standing)

Exclusion Criteria:

1. diagnosis of bulimia nervosa [DSM-5]

2. current pregnancy

3. admission for food refusal without malnutrition

4. chronic disease (e.g. immune/endocrine disorders,pulmonary, cardiac, or renal disease)

5. current suicidality or psychosis.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anorexia
• Anorexia Nervosa
• Refeeding Syndrome

Intervention

Behavioral:
• High calorie refeeding
beginning with 2000 kcal and advanced 200 kcal/d
• Low calorie refeeding
beginning at 1400 kcal/d and advanced 200 kcal every other day

Locations

Country	Name	City	State
United States	Stanford Hospital	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical remission defined by weight and medical stability	(i) weight = 95% median BMI (MBMI) for age and sex, and (ii) medical stability during 12 mo follow-up defined by published vital sign thresholds. If both of these conditions are met we will consider the patient in clinical remission.	12 months	No
Primary	Incidence of electrolyte inbalances	We will monitor any differences in LCR and HCR by incidence of: 1- hypophosphatemia (=3 mg/dL), 2- hypomagnesaemia (=1.7 mg/dL), and 3- hypokalemia (=3.5 mEq/L). If any of these three conditions occur we will record this as an instance of electrolyte inbalance.	12 months	Yes
Primary	Cost of initial and re-hospitalizations	Hospital costs, taking into account number of days in hospital and any extra services performed (blood draws, PICU consults, etc), and any rehospitalization costs.	12 months	No
Secondary	Clinical remission defined by psychological recovery	Eating Disorder Examination (EDE) global score within 1 SD of clinical norm	12 months	No
Secondary	Cost of 12 mo follow-up and other care	Cost of outpatient visits - including medical, nutrition, and psychological	12 months	No