Denosumab for Osteoporosis in Cystic Fibrosis

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: No CF diagnosis, No osteoporosis, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

Main Study Up to 100 subjects, both non-CF volunteers and Cystic Fibrosis (CF) patients, will participate in a single study visit that will include a DEXA scan, micro CT, and blood collection. Denosumab (Prolia) Sub study Approximately 10 adult subjects with CF who participated in the main study and have results indicating bone disease will receive treatment with Denosumab for up to 5 years. They will be asked to return annually for repeat DEXA scans, micro CT, and blood collection.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study coordinators for more details.

What data supports the effectiveness of the drug Denosumab for osteoporosis in cystic fibrosis?

While there is no direct data on Denosumab for cystic fibrosis-related osteoporosis, a similar drug, romosozumab, showed significant improvement in bone mineral density in a patient with cystic fibrosis. This suggests that Denosumab, which is also used to treat osteoporosis, might be effective in this context. ^{1 2 3 4 5}

Is Denosumab safe for humans?

Denosumab, also known as Prolia or Xgeva, has been studied for safety in humans for various conditions, including osteoporosis. It is generally considered safe, but like any medication, it can have side effects, so it's important to discuss with a healthcare provider. ^{3 6 7 8 9}

How is the drug Denosumab unique for treating osteoporosis in cystic fibrosis?

Denosumab is unique because it is a monoclonal antibody (a type of protein made in the lab) that works by inhibiting a protein involved in bone resorption (the process of breaking down bone), which is different from bisphosphonates like alendronate that are commonly used for osteoporosis in cystic fibrosis. This novel mechanism may offer an alternative for patients who do not respond well to other treatments. ^{1 3 7 10 11}

Research Team

Eligibility Criteria

This trial is for adults with Cystic Fibrosis (CF) who have been diagnosed with osteoporosis. Participants must be able to understand and write in English, and willing to return for annual study visits over a period of up to five years.

Inclusion Criteria

Subjects (and parents/legal guardians as applicable) must have the ability to read and write in English

My cystic fibrosis diagnosis was confirmed by a sweat test or genetic test.

Exclusion Criteria

I do not have cystic fibrosis.

I am not willing to commit to yearly study visits for 5 years.

I am under 18 years old.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Main Study

Participants undergo a single study visit including a DEXA scan, micro CT, and blood collection

1 day

1 visit (in-person)

Denosumab Sub-study

Participants with bone disease receive Denosumab treatment every 6 months and annual assessments

5 years

10 visits (in-person) over 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Denosumab (Monoclonal Antibodies)

Trial Overview The trial is testing Denosumab's effectiveness on bone disease in CF patients. It involves an initial study visit with scans and blood tests, followed by selected patients receiving Denosumab treatment annually for up to five years.

Participant Groups

Group I: Denosomab Sub-study Experimental Treatment 1 Intervention

Approximately 10 subjects with CF that have completed the main study and have results which indicate bone disease are eligible to participate in the sub study. Subjects who consent will receive treatment with denosumab (60 mg/ml via subcutaneous injection in the upper arm, upper thigh, or abdomen every 6 months) for up to 5 years. These subjects will be asked to return every 6 months for injections and annually (+/- 6 months) for up to 5 years for a DEXA scan, micro CT, and blood collection.

Group II: Main Study Active Control 1 Intervention

Up to 100 subjects, both non-CF volunteers and Cystic Fibrosis (CF) patients, will participate in a single study visit that will include a DEXA scan (if not completed as standard of care within 6 months prior to research visit), micro CT, and blood collection.

Denosumab is already approved in Canada, Japan for the following indications:

Approved in Canada as Prolia for:

• Treatment of osteoporosis in postmenopausal women at high risk for fracture
• Treatment to increase bone mass in men with osteoporosis at high risk for fracture

Approved in Japan as Prolia for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of bone loss associated with hormone ablation therapy for prostate cancer

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Findings from Research

In a study involving 171 young patients with cystic fibrosis, treatment with calcium and calcifediol improved bone mineral density in 25% of participants, indicating that proper calcium intake can be beneficial for bone health in these patients.

For those who did not respond to the initial treatment, alendronate significantly increased bone mineral density by 16.3% compared to just 3.1% in the placebo group, demonstrating its efficacy and safety in improving bone health in young individuals with cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate. Bianchi, ML., Colombo, C., Assael, BM., et al.[2022]

In a study of 56 adults with cystic fibrosis and low bone mass, alendronate therapy significantly increased lumbar spine bone mineral density (BMD) by 5.20% compared to a slight decrease in the placebo group, indicating its efficacy in improving bone health.

The treatment was well tolerated with no significant differences in quality of life or adverse events between the alendronate and placebo groups, suggesting it is a safe option for patients with cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial). Papaioannou, A., Kennedy, CC., Freitag, A., et al.[2021]

In a study of 17 young adult cystic fibrosis patients, normal bone mineral density (BMD) was observed despite abnormal bone turnover, with increased levels of bone formation markers (osteocalcin and PICP) and normal levels of bone resorption marker (ICTP).

BMD was positively correlated with pulmonary function, suggesting that better lung health may support bone health in cystic fibrosis patients, while inflammatory markers like IL-6 were inversely correlated with bone formation markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of bone mineral density and turnover in patients with cystic fibrosis: associations between the IGF system and inflammatory cytokines. Street, ME., Spaggiari, C., Ziveri, MA., et al.[2015]

In a study of 64 adults with cystic fibrosis, 52% were found to have low bone mineral density (BMD), with male sex, short stature, and low lean mass being significant predictors of this condition.

Over a 2-year period, lower lung function and higher fat mass index were linked to greater loss of BMD, highlighting the importance of maintaining lung health and lean body mass in managing bone health in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body composition, lung function, and prevalent and progressive bone deficits among adults with cystic fibrosis. Baker, JF., Putman, MS., Herlyn, K., et al.[2020]

Patients with cystic fibrosis are at a higher risk for low bone mineral density and fragility fractures, highlighting the need for careful monitoring of bone health in these individuals.

The paper provides consensus statements based on current knowledge and expert validation, offering guidance on assessing, preventing, and treating skeletal deficits associated with cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European cystic fibrosis bone mineralisation guidelines. Sermet-Gaudelus, I., Bianchi, ML., Garabédian, M., et al.[2022]

Adults with late-stage cystic fibrosis have severely decreased bone mineral density, averaging 2 standard deviations below normal, leading to significantly higher fracture rates, particularly in younger women and middle-aged men.

Osteoporosis in these patients is associated with severe kyphosis and height loss, with cumulative prednisone use, body mass index, and age at puberty identified as key predictors of bone mineral density.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis. Aris, RM., Renner, JB., Winders, AD., et al.[2019]

Cystic fibrosis patients experience significant bone health issues, including premature osteopenia and osteoporosis, due to factors like delayed puberty, malabsorption, and corticosteroid use, leading to a higher risk of fractures and kyphosis.

Regular monitoring of bone mineral density using dual energy X-ray absorptiometry is recommended for all cystic fibrosis patients starting in adolescence, and early treatment with bisphosphonates shows promise in improving bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of lung inflammation on bone metabolism in adolescents with cystic fibrosis. Conway, SP.[2009]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy of alendronate in adults with cystic fibrosis with low bone density. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Osteoporosis in cystic fibrosis. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Romosozumab used to treat a patient with cystic fibrosis-related osteoporosis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Relation of bone mineral density with clinical and laboratory parameters in pre-pubertal children with cystic fibrosis. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial). [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Analysis of bone mineral density and turnover in patients with cystic fibrosis: associations between the IGF system and inflammatory cytokines. [2015]

8. France pubmed.ncbi.nlm.nih.gov

Body composition, lung function, and prevalent and progressive bone deficits among adults with cystic fibrosis. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

European cystic fibrosis bone mineralisation guidelines. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Impact of lung inflammation on bone metabolism in adolescents with cystic fibrosis. [2009]