Chronotherapeutic Optimization of Teriparatide Administration in Postmenopausal Osteoporosis

Chronotherapeutic Optimization of Teriparatide Administration in Postmenopausal Osteoporosis: A Randomized Controlled Exploratory Study

This is a randomized, controlled, and exploratory study designed to evaluate the chronotherapeutic effects of teriparatide administration in postmenopausal osteoporosis. Twenty-eight participants (age 60-70 years, lumbar spine T-score ≤-3.0) will undergo 1:1 randomization to receive 20 µg/day teriparatide subcutaneously at either 08:00 or 20:00 for 12 weeks. Standardized supplementation with calcium (1,000-1,500 mg/day) and cholecalciferol (800-1,200 IU/day) will be maintained. Primary endpoints are between-group differences in serum CTX and P1NP profiles, quantified at baseline, 4-week interim, and 12-week endpoint. The secondary outcomes will assess safety during the trial.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteoporosis; Circadian Rhythm Disorders
• Intervention / Treatment: Behavioral: Morning administration group of teriparatide; Behavioral: Evening administration group of teriparatide

Detailed Description

This is a randomized, controlled, and exploratory study designed to evaluate the chronotherapeutic effects of teriparatide administration in postmenopausal osteoporosis. The trial protocol was approved by the Peking University Third Hospital Medical Science Research Ethics Committee. This trial intends to enroll postmenopausal osteoporosis patients admitted to the Department of Orthopedics of Peking University Third Hospital. Subjects who meet the inclusion and exclusion criteria can be enrolled in this trial after signing the informed consent form. Each trial group plans to enroll 14 subjects, with a total of 28 subjects. Eligible participants will be randomly assigned (1:1) to either subcutaneous injection of 20 μg teriparatide at 08:00 a.m in the morning (Group A) and subcutaneous injection of 20 μg teriparatide at 20:00 p.m in the evening(Group B). The specific time of drug administration for each patient every day needs to be recorded in the diary card. All subjects will be given calcium (1000-1500 mg/day) and vitamin D (800-1200 IU/day) simultaneously during the trial.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Huan Wang, Dr; Phone Number: 13331151140; Email: wanghuan1004@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 60-70 years (inclusive).
2. Naturally postmenopausal women with≥5 years since last menses.
3. DXA-measured BMD T-score≤-3.0 at lumbar spine (L1-L4) and/or total hip at screening.
4. The concentration of 25-hydroxyvitamin D (25-OH)D is ≥20 ng/ml. If the subject meets all other inclusion and exclusion criteria, it is allowed to retest the 25-OHD concentration after administering vitamin D to the subject.
5. Normal-range serum parameters:

Intact PTH: 15-65 pg/mL Total calcium: 2.20-2.70 mmol/L.

Exclusion Criteria:

1. Subjects with bone metabolic diseases besides osteoporosis:

   1. Other metabolic bone diseases, such as osteomalacia, osteogenesis imperfecta, Paget's disease；
   2. Cushing's syndrome;
   3. Hyperprolactinemia;

2. Use of medications that affect bone metabolism before screening:

   Use of intravenous bisphosphonates, fluoride, or strontium within 2 years; Use of teriparatide or denosumab for osteoporosis within 6 months; Oral bisphosphonates for osteoporosis with the last dose within 1 year (if used within 1 year but with a cumulative use of ≤1 month, the subject is eligible); Continuous use of calcitonin for more than 3 months with the last dose within 1 year.

3. History of malignancy within 5 years, or bone metastasis, except for tumors that are expected to be cured after treatment (such as completely resected in situ basal cell or squamous cell carcinoma of the skin, cervical cancer, or breast ductal carcinoma, etc.).
4. Hypocalcemia and hypercalcemia.
5. Elevated alkaline phosphatase of unknown cause.
6. History of fractures.
7. Uncontrolled comorbidities, including heart failure with New York Heart Association (NYHA) functional class III or above, glycated hemoglobin >8.5%, and severe arrhythmias.
8. Allergy to teriparatide.
9. Currently participating in another drug clinical trial.
10. Subjects deemed unsuitable for enrollment in this study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Morning (8:00) administration group of teriparatide; A total of 14 subjects will be included. Teriparatide injection (20 µg, subcutaneous injection, once daily) will be administered in the morning (around 8:00 a.m.) every day for 12 weeks	Behavioral: Morning administration group of teriparatide; Eligible participants will be randomly assigned (1:1) to either subcutaneous injection of 20 μg teriparatide at 08:00 a.m. in the morning (Group A) and subcutaneous injection of 20 μg teriparatide at 20:00 p.m. in the evening (Group B).
Experimental: Evening (20:00) administration group of teriparatide; A total of 14 subjects will be included. Teriparatide injection (20 µg, subcutaneous injection, once daily) will be administered in the evening (around 20:00 p.m.) every day for 12 weeks	Behavioral: Evening administration group of teriparatide; Eligible participants will be randomly assigned (1:1) to either subcutaneous injection of 20 μg teriparatide at 08:00 a.m. in the morning (Group A) and subcutaneous injection of 20 μg teriparatide at 20:00 p.m. in the evening (Group B).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of CTX from baseline after administration	Compare the morning and evening dosing groups regarding the changes in serum CTX from baseline after 4 and 12 weeks of subcutaneous injection of teriparatide.	Within 12 weeks
Change of P1NP from baseline after administration	Compare the morning and evening dosing groups regarding the changes in serum P1NP from baseline after 4 and 12 weeks of subcutaneous injection of teriparatide.	Within 12 weeks
Change of PTH from baseline after administration	Compare the morning and evening dosing groups regarding the changes in serum PTH from baseline after 4 and 12 weeks of subcutaneous injection of teriparatide.	Within 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Evaluation	All adverse drug reactions that occurred during the trial.	Within 12 weeks

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Investigators: Principal Investigator: Chunli Song, Dr, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: April 23, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 30, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Teriparatide, osteoporosis, Chronotherapy
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Nervous System Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Chronobiology Disorders; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents; Teriparatide
• Other Study ID Numbers: M20250309

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
• product manufactured in and exported from the U.S.: No