PRebiotic to IMprovE Calcium Absorption (PRIME)

Prebiotic Intervention to Improve Calcium Absorption After Gastric Bypass Surgery

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Dietary supplement: Prebiotic: soluble corn fiber; Dietary supplement: Placebo: maltodextrin

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prebiotic: soluble corn fiber; SCF (PromotorTM Soluble Corn Fiber 85, provided by manufacturer Tate & Lyle) will be dispensed to participants as a dry powder in sachets of 12 g SCF85 product (which is approximately 10 g fiber). Participants will mix the powder into 250 mL water and consume two such beverages daily, ≥1 hour apart. (For the first week, all participants will consume one beverage daily, and subsequently increase to one beverage twice daily.) Participants will be asked to substitute these for 500 mL of their usual daily water intake but to make no other dietary changes.	Dietary supplement: Prebiotic: soluble corn fiber; prebiotic; Other Names: PROMOTOR 85
Placebo Comparator: Placebo; The placebo control will be maltodextrin powder in identical sachets. Participants will mix the powder into 250 mL water and consume two such beverages daily, ≥1 hour apart. (For the first week, all participants will consume one beverage daily, and subsequently increase to one beverage twice daily.) Participants will be requested to substitute these for 500 mL of their usual daily water intake but to make no other dietary changes.	Dietary supplement: Placebo: maltodextrin; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fractional intestinal calcium absorption	Fractional calcium absorption to be determined using dual stable isotopic tracers	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bone turnover markers	Serum biochemical markers of bone turnover C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP)	2 months
Gastrointestinal tolerability	Self-reported flatulence, bloating, abdominal pain, stomach noises	2 months
Acceptability	Self-reported satisfaction, likelihood that one would be willing to consume the beverage for 12 months	2 months
Change in gut microbiome composition	Stool bacterial and fungal composition to be analyzed, including alpha diversity and beta diversity metrics as well as taxon relative abundance, with subsequent in silico metagenomic predictions of enrichment of bacterial functional gene pathways	2 months

Collaborators and Investigators

• Sponsor: San Francisco Veterans Affairs Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of California, San Francisco
• Investigators: Principal Investigator: Anne Schafer, MD, UCSF & SFVAMC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): January 31, 2020

Study Registration Dates

• First Submitted: August 25, 2017
• First Submitted That Met QC Criteria: September 1, 2017
• First Posted (Actual): September 5, 2017

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: postmenopausal women; gastric bypass; calcium absorption
• Other Study ID Numbers: 17-22618; R21DK112126 (U.S. NIH Grant/Contract)

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