A Phase 2 interventional study of Denosumab in Gout, sponsored by University of Alabama at Birmingham. Completed at 1 site in United States. Open to participants aged 30 Years and older. Per ClinicalTrials.gov, last updated 2021-11-02.
Sponsored by University of Alabama at Birmingham · Phase 2, Interventional, and Treatment
Bone erosions are a common manifestation and feature of structural damage in severe/chronic tophaceous gout. Management of this destructive and often debilitating gout complication has focused exclusively on urate-lowering therapy (ULT) to reduce frequency of gout attacks, but little attention has been given to prevention or reversal of gout related bone erosions and other structural damage to bone caused by gout. Since there is no known effective treatment to attenuate or improve structural damage caused by gout, we propose a pilot, controlled, proof-of-concept study in which denosumab, an FDA approved medication for the treatment of bone loss, will be added to standard ULT in 20 patients with erosive gout.
A recently published clinical trial with zoledronic acid failed to show an effect in improving bone erosions among individuals with chronic tophaceous gout, despite improvements in bone mineral density (BMD) and bone turnover markers. However, it is known that increased numbers of osteoclasts (cells that absorb bone tissue during growth and healing) in patients with tophaceous gout are most likely a result of enhanced osteoclast activity as these patients also have higher circulating levels of the protein receptor activator of nuclear factor kappa-B ligand (RANKL). RANKL has been identified to affect the immune system and control bone regeneration and remodeling.
Furthermore, peripheral blood cells and synovial fluid cells taken from patients with erosive gout preferentially formed osteoclast-like cells in the presence of RANKL. The number of osteoclasts formed significantly correlates with the number of tophi in gout patients.
Denosumab (Prolia®) is a fully human monoclonal antibody with a high affinity for RANKL that can bind and neutralize the activity of human RANKL. Given the relevance of RANKL in the mechanism of gouty erosions,a central hypothesis of this pilot study is that denosumab is more likely to precisely target RANKL and the mechanism of gouty erosions than zoledronic acid.
232 studies on the registry are indexed under Gout; 45 are open to participants now.
This study's enrollment of 20 is below the median of 121 across 202 interventional studies indexed under Gout.
Browse Gout studies →University of Alabama at Birmingham is the lead sponsor of 1,396 studies on the registry; 284 are open to participants now.
Of its 156 completed or terminated interventional studies of FDA-regulated products, 124 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care
Drug: Denosumab
Standard urate lowering therapy
Participants will be randomized (1:1) allocation to denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + ULT standard of care OR ULT standard of care therapy
Also known as: Prolia
CT Bone Erosion Score
Change in the foot CT bone erosion score from baseline to 12 months. A total of 14 bones of the foot are scored. Each bone of the scored separately on a scale from 0 to 10, based on the proportion of eroded bone compared with the 'assessed bone volume', judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2: 11-20% bone eroded; 3:21-30% of bone eroded; 4: 31-40% of bone eroded; 5: 51-60% bone eroded; 7:61-70% of bone eroded; 8: 71-80% of bone eroded; 9: 81-90% bone eroded; 10:\>=91% of bone eroded. Higher score indicates worsening of erosion. Score ranges from 0 to 140.
Time frame: Baseline, 12 months
Decrease in Bone Reabsorption
Change in bone reabsorption as measured by serum carboxy-terminal collagen crosslinks (CTX) levels (pg/mL) over 12 months. Lower values represent varying degrees of suppression of normal bone turnover. The reference ranges for C-terminal telopeptide in serum are as follows: Female (premenopausal): 40-465 pg/mL Female (postmenopausal): 104-1008 pg/mL Male: 60-700 pg/mL
Time frame: Baseline, 12 months
Change in Subject Reported Functional Status (Disability)
Change in subject reported functional status (disability) by Health Assessment Questionnaire (HAQ) will be assessed from baseline over 12 months. 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 moderate to severe disability, and 2 to 3 severe to very severe disability.
Time frame: Baseline, 12 months
Subject Reported Change in Physical Health
Subject reported change in physical and mental health by Short Form Health Survey (SF-12) scores assessed from baseline over 12 months. Range 0-100 with higher scores representing better self-reported health.
Time frame: Baseline, 12 months
Subject Reported Change in Mental Health
Subject Reported Change in Mental Health on SF-12 mental component form. Range 0-100 with higher scores representing better self-reported health
Time frame: Baseline, 12 months
Assessment of Pain
Assessment of pain score by visual analogue scale (VAS) reported from baseline over 12 months. Range 0-10 with higher scores representing more pain.
Time frame: Baseline, 12 months
Potential study participants were screened for enrollment at rheumatology clinics located at the University of Alabama at Birmingham and the University of Auckland. Participants were recruited between March 2017 and May 2019.
| Milestone | Intervention | Control |
|---|---|---|
| Started | 10 | 10 |
| Completed | 10 | 10 |
| Not completed | 0 | 0 |
Change in the foot CT bone erosion score from baseline to 12 months. A total of 14 bones of the foot are scored. Each bone of the scored separately on a scale from 0 to 10, based on the proportion of eroded bone compared with the 'assessed bone volume', judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2: 11-20% bone eroded; 3:21-30% of bone eroded; 4: 31-40% of bone eroded; 5: 51-60% bone eroded; 7:61-70% of bone eroded; 8: 71-80% of bone eroded; 9: 81-90% bone eroded; 10:\>=91% of bone eroded. Higher score indicates worsening of erosion. Score ranges from 0 to 140.
| Score on a scale | Intervention | Control |
|---|---|---|
| CT Bone Erosion Score | 6.6 ± 5.4 | 7.0 ± 5.1 |
Change in bone reabsorption as measured by serum carboxy-terminal collagen crosslinks (CTX) levels (pg/mL) over 12 months. Lower values represent varying degrees of suppression of normal bone turnover. The reference ranges for C-terminal telopeptide in serum are as follows: Female (premenopausal): 40-465 pg/mL Female (postmenopausal): 104-1008 pg/mL Male: 60-700 pg/mL
| pg/mL | Intervention | Control |
|---|---|---|
| Decrease in Bone Reabsorption | 177.6 ± 143.1 | 324.1 ± 113.3 |
Change in subject reported functional status (disability) by Health Assessment Questionnaire (HAQ) will be assessed from baseline over 12 months. 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 moderate to severe disability, and 2 to 3 severe to very severe disability.
| Difference in HAQ score from baseline | Intervention | Control |
|---|---|---|
| Change in Subject Reported Functional Status (Disability) | .33 ± .30 | .11 ± 0.24 |
Subject reported change in physical and mental health by Short Form Health Survey (SF-12) scores assessed from baseline over 12 months. Range 0-100 with higher scores representing better self-reported health.
| units on a scale | Intervention | Control |
|---|---|---|
| Subject Reported Change in Physical Health | 45.5 ± 12.6 | 52.3 ± 1.8 |
Subject Reported Change in Mental Health on SF-12 mental component form. Range 0-100 with higher scores representing better self-reported health
| units on a scale | Intervention | Control |
|---|---|---|
| Subject Reported Change in Mental Health | 58.7 ± 6.7 | 53.1 ± 7.6 |
Assessment of pain score by visual analogue scale (VAS) reported from baseline over 12 months. Range 0-10 with higher scores representing more pain.
| units on a scale | Intervention | Control |
|---|---|---|
| Assessment of Pain | 1.3 ± 3.1 | 1.2 ± 1.4 |
Collected over 1 year. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Intervention | 0/10 (0%) | 0/10 (0%) | 5/10 (50%) |
| Control | 0/10 (0%) | 0/10 (0%) | 6/10 (60%) |
| Event | Intervention | Control |
|---|---|---|
| Atrial flutterCardiac disorders | 0/10 | 1/10 |
| Atrial fibrillationCardiac disorders | 1/10 | 0/10 |
| Gastro-esophageal refluxGastrointestinal disorders | 0/10 | 1/10 |
| VomittingGastrointestinal disorders | 1/10 | 0/10 |
| Esophageal refulxGastrointestinal disorders | 0/10 | 1/10 |
| Back PainMusculoskeletal and connective tissue disorders | 0/10 | 1/10 |
| Joint PainMusculoskeletal and connective tissue disorders | 1/10 | 1/10 |
| CrampsMusculoskeletal and connective tissue disorders | 1/10 | 0/10 |
| Skin RashSkin and subcutaneous tissue disorders | 1/10 | 0/10 |
| AnemiaBlood and lymphatic system disorders | 0/10 | 1/10 |
| Age, Continuous(years) | Intervention | Control | Total |
|---|---|---|---|
| Mean | 67 ± 15 | 63 ± 9.4 | 65.0 ± 12.4 |
| Sex: Female, Male(Participants) | Intervention | Control | Total |
|---|---|---|---|
| Female | 1 | 0 | 1 |
| Male | 9 | 10 | 19 |
| Race/Ethnicity, Customized(Participants) | Intervention | Control | Total |
|---|---|---|---|
| European descent | 6 | 5 | 11 |
| Maori | 0 | 2 | 2 |
| Asian | 1 | 1 | 2 |
| Pacific Islander | 0 | 0 | 0 |
| Other | 3 | 2 | 5 |
| Region of Enrollment(Participants) | Intervention | Control | Total |
|---|---|---|---|
| United States | 5 | 4 | 9 |
| New Zealand | 5 | 6 | 11 |
| Serum Urate(mg/dL) | Intervention | Control | Total |
|---|---|---|---|
| Mean | 4.3 ± 0.5 | 4.2 ± 0.7 | 4.3 ± 0.6 |
| Estimated glomerular filtration rate(mL/min/1.73m2) | Intervention | Control | Total |
|---|---|---|---|
| Mean | 76.5 ± 32 | 72 ± 15.3 | 74.2 ± 24.5 |
| CT Erosion Score (range 0-140 total of 14 bones)(units on a scale) | Intervention | Control | Total |
|---|---|---|---|
| Mean | 6.6 ± 5.4 | 7.0 ± 5.1 | 6.8 ± 5.1 |
| Serum CTX(pg/mL) | Intervention | Control | Total |
|---|---|---|---|
| Mean | 316.6 ± 152.6 | 286.9 ± 111.5 | 303.4 ± 133.0 |
4 further baseline measures are reported on the registry.
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University of Alabama at Birmingham