Denosumab (DMAB) Discontinuation And Switching In Glucocorticoid-Induced Osteoporosis (GIOP): A Pilot Study

  • STATUS
    Recruiting
  • End date
    Aug 31, 2024
  • participants needed
    45
  • sponsor
    University of Alabama at Birmingham
Updated on 26 December 2021

Summary

Investigators will test the hypothesis that an increase in bone turnover markers (e.g. carboxy-terminal collagen crosslinks (CTX) and P1NP) in patients currently taking chronic glucocorticoids will be attenuated more in those who switch from denosumab to "late" zoledronic acid (9 months after last denosumab dose) compared to participants randomized to "early" zoledronic acid (6 months after last denosumab dose) or weekly alendronate (6 months after last denosumab dose).

Description

This is an open-label, randomized, parallel-group pilot clinical trial in which Denosumab users will be assigned in a 1:1:1 allocation to one the following groups:

  • Switch from Denosumab 60 mg administered subcutaneously (SC) to weekly oral alendronate (70 mg; started 6 months after last denosumab dose) OR
  • Switch from Denosumab 60 mg administered subcutaneously (SC) to one "early" zoledronic acid infusion (5 mg; 6 months after last denosumab dose) OR
  • Switch from Denosumab 60 mg administered subcutaneously (SC) to one "late" zoledronic acid infusion (5 mg; 9 months after last denosumab dose)

Participants will be advised to maintain adequate calcium and vitamin D intake per United States Department of Agriculture (USDA) and Department of Health and Human Services (DHHS) guidelines. All individuals will need 12 months of previous denosumab treatment (minimum of 2 doses) prior to switching to assigned randomization arm. The minimum number of doses (n = 2) is based on published data that the rebound in BMD might be less pronounced in patients receiving very limited denosumab. According to a systematic review of patients with multiple vertebral fractures following denosumab cessation, those with 2 years of denosumab treatment had fewer fractures compared with those with >2 years. Therefore, the maximum number of prior doses (n = 4) is based on higher incidence of rebound loss of bone mineral density (BMD), more rapid turnover, and potentially greater vertebral fractures after discontinuation of denosumab in patients who received more extensive treatment. Investigators will limit the trial to a more restricted use of denosumab duration (2-4 doses) to maintain greater homogeneity, given the somewhat smaller planned sample size. Users of denosumab will be sorted into two groups:

  • Prevalent users: Defined as individuals with a minimum of one previous dose of denosumab, and up to 4 previous doses of denosumab (maximum). Prevalent users with one previous dose will receive a second dose of denosumab before proceeding to assigned randomization arm. Therefore, randomization will occur 2 weeks after screening visit if they had already 2-4 denosumab doses.
  • New denosumab users: Defined as individuals who have not previously received denosumab. New users will receive two doses of denosumab before proceeding to assigned randomization arm.

Details
Condition Osteopenia, Osteopenia, Osteoporosis, Osteoporosis
Treatment DMAB Discontinuation and Switching
Clinical Study IdentifierNCT04177940
SponsorUniversity of Alabama at Birmingham
Last Modified on26 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Women and men, age 18 years or older and able to provide informed consent (IC)
months of glucocorticoid use at > 7.5 mg /day (prednisone equivalent dose) and anticipated to remain on glucocorticoids for at least six months
A baseline BMD T-score of -2.0 at the lumbar spine, total hip, or femoral neck; OR
A BMD T-score -1.0 at the lumbar spine, total hip, or femoral neck and a history of an osteoporotic fracture

Exclusion Criteria

Patients with fewer than three lumbar vertebrae that could be evaluated on dual energy x-ray absorptiometry (DXA)
Treatment with bisphosphonates in the preceding 2 years
Greater than 24 months (>4 injections) of prior treatment with denosumab
Women of childbearing potential, who are not currently using birth control, are pregnant, planning to become pregnant, or are breastfeeding. For women of childbearing potential: refusal to use 2 highly effective forms of contraception and to continue this practice for 7 months after last injection of study medication
Men planning to conceive in the next 12 months
Unstable systemic medical condition
Uncontrolled hyperthyroidism
Uncontrolled hypothyroidism
History of Addison disease
History of osteomalacia
History of osteonecrosis of the jaw (ONJ)
History of atypical femur fracture
History of tooth extraction, jaw surgery, dental implants, or other dental surgery within the prior 6 months
History of anorexia nervosa, bulimia (by history or physical) or obvious malnutrition
Invasive dental work(implants/surgery) planned in the next 2 years
History of Paget's disease of bone
Other bone diseases which affect bone metabolism
Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)]
Hypercalcemia >10% above upper limit of normal (ULN)
Elevated transaminases or total bilirubin 2.0 x ULN
History of any solid organ or bone marrow transplant
Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma or localized squamous cell carcinoma of the skin)
Hypocalcemia <10% below lower limit of normal (LLN)
Estimated glomerular filtration rate < 30 mL/minute/1.73 m^2
Intolerance to calcium supplements, vitamin D supplements
Contraindication to, or poorly tolerant of denosumab therapy (including hypersensitivity to the drug)
Contraindication to, or poorly tolerant of zoledronic therapy (including hypersensitivity to the drug)
Contraindication to, or poorly tolerant of alendronate (including hypersensitivity to the drug and sever gastro-intestinal intolerance to oral bisphosphonates)
Recipient of an investigational drug within 4 weeks prior to study drug administration
Not a good candidate for study participation in opinion of investigator
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note