Clinical trial NCT02557438: Effects of Weight Loss Surgery on Bone Health in Adolescents
Official title: Bone Metabolism in Adolescents Undergoing Bariatric Surgery
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Obesity
Surgery
Keywords: Bone
Child Health
Nutrition
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2015-09-23
Enrollment: 240
Sex: ALL
Minimum age (years): 13
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adolescents and young adults 13-25 years old with obesity undergoing RYGB or VSG and non-surgical controls.

Brief summary: The purpose of this study is to examine the impact of weight-loss surgery (Roux-en-Y gastric bypass or Vertical Sleeve Gastrectomy) on bone outcomes in girls and boys ages 13-21. This study will also examine a group of overweight boys and girls who are not scheduled or planned for surgery for comparison of these outcomes.

Obese adults who undergo weight-loss surgery are at risk for bone loss and decreased bone strength. The investigators do not know the effects of such surgery on bone in teenagers and young adults. The purpose of this study is to find out how different types of weight loss surgery affect bone density and strength in teenagers and young adults and compare these results to obese teenagers and young adults who are not undergoing weight-loss surgery.

Detailed description: Our overall hypothesis is that both Roux-en-Y Gastric Bypass (RYGB) and vertical sleeve gastrectomy (VSG) in adolescents with morbid obesity will lead to a reduction in areal and volumetric BMD, and deterioration in bone structure and estimated bone strength, and an increase in marrow adiposity. We further hypothesize that these effects will be due in part to a decrease in lean mass, changes in enteric peptide hormones and reduced estrogen levels.

We will enroll 120 participants 13-21 years old for this two-year longitudinal study (36 in each of the surgical groups and 48 non-surgical controls with obesity). We will screen up to 240 subjects to find these 120 eligibile subjects. Areal bone mineral density (BMD) will be assessed by dual energy x-ray absorptiometry (DXA), volumetric BMD by quantitative computed tomography (QCT), bone structure and strength using high resolution peripheral QCT and finite element analysis, and marrow fat using magnetic resonance spectroscopy. Body composition will also be assessed.

Adolescence is a critical time for bone accrual and the use of bariatric procedures is increasing in teenagers. This study will provide novel data needed to establish effects of RYGB vs. VSG on bone in adolescents and will begin to delineate underlying mechanisms. Clarifying these mechanisms will identify therapeutic targets to optimize bone accrual in adolescents undergoing bariatric surgery.

Eligibility criteria: Inclusion Criteria:

1. Adolescents with morbid obesity 13-25yo undergoing RYGB (n=36) or VSG (n=36), or being followed without surgical intervention (usual care) (n=48).
2. Eligibility criteria for weight loss surgery used at the Weight Center include BMI\>40 or BMI\>35kg/m2 with major comorbidities. A BMI\>35 in adolescents reflects a BMI\>99th percentile. In order to be considered appropriate surgical candidates, children must have a bone age of ≥14y (F) or ≥16y (M), and ≥1 co-morbidity of obesity. They must have demonstrated efforts at non-surgical weight loss, and consistent compliance with appointments and recommendations. Patients must demonstrate sufficient maturity, psychological stability and cognitive capacity to recognize the significance of the procedure and implement required post-operative behavioral changes.

Exclusion Criteria:

1. Current pregnancy and breast feeding
2. Medications other than calcium or vitamin D that affect bone, such as glucocorticoids, phenytoin, phenobarbitone (washout of 3 months prior to enrollment if discontinuation is medically permissible)
3. Use of antipsychotic medications that cause weight gain if treated for \<6 mos, or if dosage is not stable for \>2 mos
4. Untreated thyroid dysfunction or on stable dose for \<3 mos
5. HbA1C\>8% (to avoid deleterious effects on bone from uncontrolled T2DM)
6. Smoking \>10 cigarettes/day; substance abuse per Diagnostic and Statistical Manual (DSM) V
7. Metal implants, intracranial surgical clips or pacemakers
8. Weight \>450 lbs due to limits for MRI and CT.

Primary outcomes:
measure: Baseline to 24 months change in total and trabecular volumetric BMD (vBMD) (distal radius and tibia)
timeFrame: 2 years
Secondary outcomes:
measure: Baseline to 24 month change in bone turnover markers (P1NP and CTX)
timeFrame: 2 years
measure: Baseline to 24 month change in estimated strength measures (FEA of distal radius and tibia)
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Madhu Misra, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Miriam Bredella, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nimmala S, Kaur S, Singhal V, Mitchell DM, Stanford FC, Bouxsein ML, Lauze M, Huynh C, Pedreira CC, Lee H, Bredella MA, Misra M. Changes in Sex Steroids and Enteric Peptides After Sleeve Gastrectomy in Youth in Relation to Changes in Bone Parameters. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3747-e3758. doi: 10.1210/clinem/dgac361.