HMB Plus Vitamin D to Preserve Muscle in Older Adults Starting Semaglutide
PRESERVE-HMB
Preserving the Metabolic Engine: HMB Supplementation to Combat Iatrogenic Sarcopenia and Metabolic Adaptation in Older Adults Initiating Semaglutide Therapy
2 other identifiers
interventional
90
1 country
1
Brief Summary
This randomized, double-blind, placebo-controlled trial will evaluate whether daily calcium beta-hydroxy-beta-methylbutyrate (calcium-HMB) plus vitamin D3 preserves muscle mass, physical function, and resting metabolism in adults aged 65 to 85 years with type 2 diabetes who are newly starting semaglutide as part of usual clinical care. Participants will receive calcium-HMB plus vitamin D3 or matching placebo for approximately 6 months. The primary outcome is change in appendicular lean mass measured by dual-energy X-ray absorptiometry from baseline to month 6. Secondary assessments include body composition, muscle strength, physical performance, gait, physical activity, resting metabolic rate, metabolic measures, and whole-body quantitative computed tomography. An optional mechanistic substudy of up to 36 participants will include D3-creatine dilution, nonradioactive stable isotope infusions, repeated blood sampling, a standardized meal, breath sampling, and vastus lateralis muscle biopsies at baseline and month 6.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Dec 2026
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 7, 2026
CompletedFirst Posted
Study publicly available on registry
August 12, 2026
CompletedStudy Start
First participant enrolled
December 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2029
Study Completion
Last participant's last visit for all outcomes
November 1, 2030
August 12, 2026
August 1, 2026
3 years
August 7, 2026
August 7, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in Appendicular Lean Mass
Appendicular lean mass will be measured by whole-body dual-energy X-ray absorptiometry. The outcome is the month-6 value minus the baseline value, reported in kilograms.
Baseline to month 6
Secondary Outcomes (22)
Title Change in Body Weight
Baseline to month 6
Change in Total Fat Mass
Baseline to month 6
Title Change in Visceral Adipose Tissue
Baseline to month 6
Change in Bone Mineral Density
Baseline to month 6
Change in Trabecular Bone Score
Baseline to month 6
- +17 more secondary outcomes
Study Arms (2)
Calcium-HMB Plus Vitamin D3
EXPERIMENTALParticipants receive active calcium-HMB plus vitamin D3 for approximately 6 months while semaglutide is prescribed and managed as standard clinical care.
Matching Placebo
PLACEBO COMPARATORParticipants receive matching placebo for approximately 6 months while semaglutide is prescribed and managed as standard clinical care.
Interventions
Each active capsule contains 750 mg calcium-HMB and 200 IU vitamin D3. Participants take two capsules twice daily, providing 3 g calcium-HMB and 800 IU vitamin D3 per day, for approximately 6 months.
Participants take two matching placebo capsules twice daily for approximately 6 months. Placebo capsules are matched to active product in appearance, packaging, labeling, and dosing schedule. Insert the final placebo ingredients if the PRS administrator requests them.
Eligibility Criteria
You may qualify if:
- Age 65 to 85 years, inclusive.
- Type 2 diabetes mellitus, defined by HbA1c at or above 6.5% or current use of antihyperglycemic medication.
- Body mass index at or above 27 kg/m2.
- Newly initiating semaglutide as standard clinical care under the direction of a treating clinician.
- Able to walk 400 meters without assistance; use of a cane is permitted.
- Able to understand and provide legally effective informed consent.
- English speaking for the initial study because the consent documents, questionnaires, study-product instructions, safety instructions, and procedure-specific materials are available only in English.
You may not qualify if:
- Estimated glomerular filtration rate below 45 mL/min/1.73 m2.
- Use of HMB, creatine, or high-dose whey protein supplements within the previous 3 months.
- Weight change greater than 5% during the previous 3 months.
- Recent fracture within the previous 6 months.
- Neuromuscular disease, including Parkinson disease, or another condition that would interfere with study outcomes or safe participation.
- Chronic corticosteroid use.
- Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.
- History of pancreatitis.
- Smoking more than 7 cigarettes per day.
- Previous malabsorptive or restrictive intestinal surgery or a malabsorptive syndrome.
- Pregnancy or breastfeeding.
- Recent history of neoplasia within the previous 5 years, as defined by the protocol.
- Other active inflammatory conditions or neuromuscular disorders that could interfere with study outcomes or safety.
- Serum 25-hydroxyvitamin D below 15 ng/mL.
- Any medical, functional, laboratory, medication-related, or safety condition that the investigator determines makes study participation unsafe or prevents completion of essential procedures.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robb Flynn, PhD
Vanderbilt University Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- TSI/MTI or its designated independent code custodian maintains the treatment code. Active and placebo products are matched in appearance, packaging, labeling, and dosing schedule. Participants, the principal investigator, study coordinators, outcome assessors, and primary analysts remain blinded except for authorized personnel requiring access for product accountability or emergency safety unblinding.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
August 7, 2026
First Posted
August 12, 2026
Study Start (Estimated)
December 1, 2026
Primary Completion (Estimated)
November 30, 2029
Study Completion (Estimated)
November 1, 2030
Last Updated
August 12, 2026
Record last verified: 2026-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- The funded plan describes sharing deidentified datasets within 6 months after publication or within 18 months after the funding period ends if unpublished. Confirm that this remains the final institutional commitment before entering it.
- Access Criteria
- Access will require repository review and any required data-use agreement, institutional approval, and agreement to use the data only for an approved research purpose and not to attempt participant reidentification.
Deidentified participant-level data underlying reported results may be shared through a controlled-access repository, including the NIDDK Central Repository or Vivli, as permitted by informed consent, HIPAA authorization, IRB approval, repository requirements, and institutional agreements. Direct identifiers will not be shared.