PTH And Calcium Responses to Exercise in Older Adults Experiment 2 (PACE Sr. 2)

Declines in serum calcium during exercise may cause increases in markers of bone resorption. This study will determine if preventing the decline serum ionized calcium experienced at the onset of exercise through the use of a "calcium clamp" also prevents increases in blood biomarkers associated with bone resorption.

Study Overview

• Status: Recruiting
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: Calcium Chloride/Calcium Gluconate; Drug: Placebo

Detailed Description

Participants will undergo two identical walking exercise sessions on a treadmill. One session will occur until continuous calcium infusion and the other will be under continuous saline infusion. C-telopeptide, parathyroid hormone, total calcium, and serum ionized calcium will be monitored to distinguish differences in bone activity under the two conditions.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Sarah J Wherry, PhD; Phone Number: 303-724-1927; Email: sarah.wherry@ucdenver.edu
• Study Contact Backup: Name: Toby Wellington, BS; Phone Number: 720-848-6376; Email: Toby.Wellington@ucdenver.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital
      • Contact: Sarah Wherry, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy adults aged 60-80 y
• Currently taking a bisphosphonate medication

Exclusion Criteria:

• Use of medications (other than bisphosphonates) in the past 6 months known to affect bone metabolism (e.g., thiazide diuretics, oral glucocorticoids)
• Bone Mineral Density (BMD) t score < -3.0 at the total hip or lumbar spine
• Known disease or condition associated with intestinal malabsorption
• Moderate or severe renal impairment defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2 based on the Modified Diet in Renal Disease (MDRD) equation
• Chronic hepatobiliary disease, defined as liver function tests (AST, ALT) >1.5 times the upper limit of normal; if such values are obtained on initial screening and thought to be transient in nature, repeated testing will be allowed
• Thyroid dysfunction, defined as an ultrasensitive TSH <0.5 or >5.0 mU/L; volunteers with abnormal TSH values will be re-considered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement
• Serum calcium <8.5 or >10.3 mg/dL Serum 25(OH)D <20 ng/mL; volunteers with abnormal serum 25(OH)D values may be re-considered for participation in the study if serum 25(OH)D is >20 ng/mL after vitamin D supplementation
• Uncontrolled hypertension defined as resting systolic BP >150 mmHg or diastolic BP>90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including after follow-up evaluation by the PCP with initiation or adjustment of anti-hypertensive medications
• History of type 1 or type 2 diabetes
• Cardiovascular disease; subjective or objective indicators of ischemic heart disease (e.g., angina, ST segment depression) or serious arrhythmias at rest or during the graded exercise test (GXT) without follow-up evaluation will be cause for exclusion; follow-up evaluation must include diagnostic testing (e.g., stress echocardiogram or thallium stress test) with interpretation by a cardiologist
• Diagnosis or history of asthma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calcium Infusion; Continuous calcium infusion during exercise	Drug: Calcium Chloride/Calcium Gluconate; Calcium (as either calcium chloride or calcium gluconate in half normal saline) will be delivered via IV during exercise to keep serum ionized calcium levels above baseline. The clamp is modeled after the hyperglycemic glucose clamp.
Placebo Comparator: Saline Infusion; Continuous saline infusion during exercise	Drug: Placebo; Saline Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Parathyroid Hormone (PTH)	PTH will be measured during baseline, throughout exercise, and during recovery at regular intervals. The investigators are looking to see how PTH changes over the course of the exercise and recovery period in both the calcium and saline. The investigators anticipate that PTH will be higher in the saline condition versus the calcium. The investigators expect that men and women will respond similarly.	At baseline, through 60 minutes of exercise, and during 4 hours of recovery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in C-telopeptide (CTX)	CTX will be measured during baseline, throughout exercise, and during recovery at regular intervals. The investigators are looking to see how PTH changes over the course of the exercise and recovery period in both the calcium and saline. The investigators anticipate that CTX will be higher in the saline condition versus the calcium. The investigators expect that men and women will respond similarly.	At baseline, through 60 minutes of exercise, and during 4 hours of recovery
Change in Total Calcium (Ca)	Total Ca will be measured during baseline, throughout exercise, and during recovery at regular intervals. The investigators are looking to see how Ca changes over the course of the exercise and recovery period in both the calcium and saline conditions.	At baseline, through 60 minutes of exercise, and during 4 hours of recovery

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Sarah J Wherry, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: October 16, 2015
• First Submitted That Met QC Criteria: October 16, 2015
• First Posted (Estimated): October 20, 2015

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Calcium
• Other Study ID Numbers: 15-0878; UM1TR004399 (U.S. NIH Grant/Contract)