Scoliosis Iron Supplementation Study

Study Overview
=================
Brief Summary
-----------------
This study is a randomized controlled trial of preoperative oral iron supplementation, to identify whether iron deficiency is a modifiable risk factor for adverse surgical outcomes such as red blood cell transfusion and diminished postoperative cognitive and physical capacity in adolescents undergoing scoliosis surgery. Research Question(s)/Hypothesis(es): Primary Iron supplementation will reduce the incidence of perioperative RBC transfusion in iron deficient scoliosis patients undergoing spinal fusion. Secondary Iron supplementation will reduce postoperative neurocognitive functional declines in iron deficient scoliosis patients undergoing spinal fusion. Iron supplementation will improve patient-reported physical functioning in iron deficient scoliosis patients undergoing spinal fusion.

Detailed Description
-----------------
Adolescents undergoing spinal fusion surgery for scoliosis are poised to benefit from preoperative iron supplementation. Spinal fusion carries a risk of large surgical blood losses and perioperative red blood cell transfusion, which are associated with adverse outcomes in this population. These patients are mostly adolescent females, a group more susceptible to iron deficiency and resulting anemia at baseline due to iron losses with menses, and who suffer an additional insult to iron stores during surgery. Nevertheless, iron status is not routinely monitored in this setting and there is no standard of care for preoperative iron supplementation. Iron is a nutritionally essential trace element important not only for red blood cell production, but also for muscle function and neurotransmitter synthesis and signaling. Therefore, the treatment of preoperative iron deficiency is an important target for optimizing hemoglobin prior to surgery, reducing transfusion rates and associated complications such as alloimmunization, and improving patient outcomes. On its own and as the primary cause of anemia, iron deficiency was identified by the investigator's team as the only risk factor for transfusion which is modifiable preoperatively. In addition, iron supplementation is shown to alleviate impairments of physical and cognitive capacity associated with even mild forms of iron deficiency in adolescent females. A pilot study conducted at the investigator's institution identified iron deficiency in 36% of scoliosis patients prior to surgery, with preoperative iron status highly correlated with iron status during surgical recovery. Consequently, the investigator plans to examine iron deficiency as a modifiable risk factor for transfusion and impaired postoperative cognitive and physical capacity in this vulnerable population. Previous trials of brief iron interventions in high-risk adult surgical patients, mostly with unknown iron status, do not inform the care of iron deficient adolescents and were not designed to address postoperative functional outcomes. This study will therefore perform a single-center randomized controlled trial in which adolescents with scoliosis will be screened for iron deficiency (n =  275), and iron-deficient adolescents with scoliosis (n =  90) will be randomized to a preoperative regimen of daily oral iron or placebo, to test the hypotheses that preoperative iron supplementation 1) reduces the rate of red blood cell transfusion, 2) improves postoperative neurocognition compared to a preoperative baseline, and 3) improves patient-reported physical functioning during recovery. Results will ultimately improve outcomes in this vulnerable pediatric population and provide evidence for patient blood management approaches to reduce transfusions amid recent severe blood shortages.

Official Title
-----------------
Study of Iron Supplementation in Adolescents Undergoing Scoliosis Surgery

Conditions
-----------------
Adolescent Idiopathic Scoliosis, Neuromuscular Scoliosis, Perioperative/Postoperative Complications, Iron Deficiencies, Anemia, Spinal Fusion, Postoperative Cognitive Dysfunction

Intervention / Treatment
-----------------
* Dietary Supplement: Oral ferrous sulfate
* Dietary Supplement: Oral placebo tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 12-19 years old diagnosis of scoliosis ability to swallow a tablet spinal fusion procedure planned at least 13 weeks from when patient agrees to phlebotomy for screening blood work serum ferritin less than or equal to 25 µg/L Exclusion Criteria: taking or planning to take iron-containing supplement under the direction of a health care provider, or under patient's own volition and and not willing to stop for duration of study C-reactive protein > 10 mg/L receiving nutritional support self-reported history of hypersensitivity reaction to iron-containing supplements self-reported history of or suspected non-iron deficient hematologic disorder self-reported history of iron overloaded state such as hereditary hemochromatosis or hemosiderosis objection to receiving red blood cell transfusions current pregnancy (by self-report) prisoners patient or parent decides against study participation

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind placebo-controlled randomized controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral ferrous sulfate<br>Participants will receive oral ferrous sulfate tablets, 325mg (65mg elemental iron). Tablets are to be taken once daily for 3-6 months prior to surgery as time allows. | Dietary Supplement: Oral ferrous sulfate<br>* Oral ferrous sulfate 325mg is used as a dietary supplement providing 65mg elemental iron.<br>|
| Placebo Comparator: Oral placebo tablets<br>Participants will receive placebo tablets. Tablets are to be taken once daily for 3-6 months prior to surgery as time allows. | Dietary Supplement: Oral placebo tablet<br>* Oral placebo tablet provided as placebo comparator.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of perioperative RBC transfusion in iron deficient scoliosis patients undergoing spinal fusion | The patients that received a red blood cell transfusion either during procedure or postoperatively during t surgical hospitalization will be tallied. | 4 to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients that experienced postoperative decline in neurocognitive function | The Cognitive Battery of the NIH Toolbox is a brief, valid, and reliable instrument designed to provide outcome measures in epidemiologic and longitudinal research that can be used for comparisons across a wide range of studies and populations. Individual measure scores in the battery reflect Executive Function, Attention, Verbal and Nonverbal Memory, Language, Processing Speed, and Working Memory, yielding composite score. A decline of function is measured by comparing the mean change from baseline in the Cognitive Function Composite Scores in the study groups. | 4-6 months | 
| Percentage of patients that experienced postoperative decline in self-reported physical capacity | The PROMIS pediatric measures are a NIH Roadmap initiative to provide access to valid and reliable self-reported measures of health-related quality of life in children and adolescents. The PROMIS measures are scored on a T-score metric with a mean of 50 and SD of 10 in the general population in the United States. Higher PROMIS symptom scores indicate increased symptom burden, and higher PROMIS function scores indicate increased functioning. Decline would be identified through a mean change (decrease) from baseline in the Physical Functioning - Mobility scores; with secondary hypotheses for Physical Functioning - Upper Extremity, Physical Activity, and Fatigue. | 4-6 months | 
| Volume of perioperative RBC transfusion | The volume that each patient receives either during procedure or postoperatively during surgical hospitalization will be summed and average calculated. | 4 to 30 days |