Clinical trial NCT03272542: PRebiotic to IMprovE Calcium Absorption
Official title: Prebiotic Intervention to Improve Calcium Absorption After Gastric Bypass Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Keywords: gastric bypass
calcium absorption
postmenopausal women
Lead sponsor: San Francisco Veterans Affairs Medical Center
Sponsor class: FED
Collaborators: name: University of California, San Francisco
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-09-05
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo-controlled pilot trial with a parallel-arm design
Primary purpose: OTHER

Brief summary: Gastric bypass surgery is a highly effective treatment for obesity, but it has negative effects on skeletal health, due in part to a dramatic decline in intestinal calcium absorption capacity. Animal and human studies suggest that non-digestible fibers termed prebiotics, such as soluble corn fiber (SCF), augment calcium absorption in the lower intestine as they act as substrates for beneficial gut microbiota. This is a pilot randomized controlled trial of the effects of SCF vs. placebo on intestinal calcium absorption, bone turnover marker levels, and the gut microbiome in postmenopausal women who have previously undergone gastric bypass surgery.

Detailed description: The study is a pilot randomized control trial (RCT) of the effects of the prebiotic SCF vs. placebo in 20 postmenopausal women who underwent Roux-en-Y gastric bypass surgery 2-6 years previously and thus have completed the postoperative period of rapid weight loss and metabolic and dietary change. A 24 g/day dose of SCF85 (which is approximately 20 g/day fiber) will be tested, as that dose was proven effective for calcium absorption/retention in healthy postmenopausal women and adolescents. The SCF and the maltodextrin placebo will be mixed in water and consumed in divided doses twice daily for 2 months, a duration exceeding other SCF trials but remaining feasible for a pilot. The primary outcome will be change in intestinal calcium absorption, which is the efficacy outcome about which the study must collect preliminary data and from which the investigators must refine power calculations for the anticipated future trial. Because the investigators hypothesize that an increase in calcium absorption will decrease bone turnover and ultimately increase bone mineral density (BMD), the study will measure biochemical markers of bone turnover in this pilot. Secondary outcomes will be gastrointestinal tolerability and acceptability. On an exploratory basis, the study will determine effects of the prebiotic on the gut microbiome. This pilot will yield critical experience about feasibility of recruitment and adherence to the intervention and measurements.

Eligibility criteria: Inclusion Criteria:

1. Postmenopausal women (no menses for ≥4 yrs)
2. ≤ 75 yrs old,
3. Underwent Roux-en-Y gastric bypass surgery for weight loss 2-6 years prior

Exclusion Criteria:

1. Serum 25(OH)vitamin D level \<30 ng/mL (to remove the effect of vitamin D insufficiency/deficiency)\*
2. History of \>1 bariatric surgical procedure
3. Antibiotic therapy in the last 3 months
4. Regular pre- or probiotic use in the last 3 months
5. Regain of \>50% of weight loss post-bypass
6. Calculated creatinine clearance \<30 mL/min
7. Serum calcium \>10.2 mg/dL
8. Use of hormone therapy, osteoporosis pharmacotherapy, glucocorticoids, or other medications impacting calcium metabolism
9. Thyroid stimulating hormone (TSH) \<0.01 milli-international units per liter (mIU/L)

A potential participant may be excluded if she has a condition or abnormality that in the opinion of the Investigator would compromise the safety of the participant or the quality of the data.

\*Women excluded due to 25(OH)D level will be offered re-screening after vitamin D supplementation.

Primary outcomes:
measure: Change in fractional intestinal calcium absorption
timeFrame: 2 months
Secondary outcomes:
measure: Change in bone turnover markers
timeFrame: 2 months
measure: Gastrointestinal tolerability
timeFrame: 2 months
measure: Acceptability
timeFrame: 2 months
measure: Change in gut microbiome composition
timeFrame: 2 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF
state: California
Study officials:
affiliation: UCSF & SFVAMC
name: Anne Schafer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu KC, Cao S, Weaver CM, King NJ, Patel S, Kingman H, Sellmeyer DE, McCauley K, Li D, Lynch SV, Kim TY, Black DM, Shafer MM, Ozcam M, Lin DL, Rogers SJ, Stewart L, Carter JT, Posselt AM, Schafer AL. Prebiotic to Improve Calcium Absorption in Postmenopausal Women After Gastric Bypass: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2022 Mar 24;107(4):1053-1064. doi: 10.1210/clinem/dgab883.