Osteoporosis Clinical Trial
— DenosuMastOfficial title:
Interest of Denosumab Treatment in Osteoporosis Associated to Systemic Mastocytosis
Verified date | April 2024 |
Source | Assistance Publique - Hôpitaux de Paris |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The study is looking at the efficacy of subcutaneously administrated denosumab 60 mg every 6 months versus placebo after 3 years, by analyze of lumbar spine bone mineral density (BMD) in systemic mastocytosis. Investigators hypothesize that use of denosumab subcutaneously in patients with osteoporosis related to systemic mastocytosis is effective and safe to improve bone mineral density and prevent new bone events, based on targeted specific RANKL secretion by mast cells and short half-life of denosumab.
Status | Completed |
Enrollment | 24 |
Est. completion date | March 11, 2024 |
Est. primary completion date | March 11, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Male or female >/= 18 years of age at time of informed consent - Willingness and ability to sign informed consent, comply with scheduled visits, treatment plan, laboratory tests and other study procedures. - Patient with Indolent systemic or cutaneous mastocytosis according to WHO criteria (Appendix 4) with any specific treatment including corticosteroid, chemotherapy and immunomodulating drugs. - Patient with: - osteoporosis defined as bone mineral density T score = -2.5 at the lumbar spine, OR - osteopenia defined as BMD T-score >-2,5 and = -1 at the lumbar spine and low energy fracture (defined as fractures that are associated with decreased bone mineral density. Are excluded fractures of skull, face, mandible, metacarpals, fingers, or toes, pathologic fracture, and fracture that are associated with severe trauma). (in case of osteoarthritis at the lumbar spine, the T score at left femoral neck or total left hip can be used to define osteoporosis or osteopenia) Exclusion Criteria: - Patient with aggressive mastocytosis or/and Associated Hematologic Non-Mastocytosis Disease (AHNMD) - Patient with conditions that influence bone metabolism (primitive hyperparathyroidism, hyperaldosteronism, hypercorticism, etc …) - Patient treated with intravenous bisphosphonate within 1 year prior to enrolment or with any other antiosteoporotic treatment within 3 months before enrolment. (per os bisphosphonate, strontium ranelate) Calcium and vitamin supplementation will be accepted - Patient previously treated with denosumab - Patient with hypocalcemia and/or hypo25-hydroxyvitamin D level non substituted prior enrolment - Woman without contraceptive treatment if of childbearing age. - Pregnant or breastfeeding woman - Patient with contraindication to denosumab - Patient with medical, psychiatric or other conditions that may interfere with patient safety - Patient with dental problem that need any dental surgery within 6 months after enrolment. - Patient with clearance of creatinine less than 30 mL/min/1,73m2 (MDRD) or patient receiving dialysis |
Country | Name | City | State |
---|---|---|---|
France | Jean Minjoz Hospital, Dermatology department | Besançon | |
France | Caen Hospital, Clinical haematology department | Caen | |
France | Estaing Hospital, Cellular therapy and clinical haematology department | Clermont-Ferrand | |
France | Lille CHRU Hospital, Internal medicine and clinical immunology department | Lille | |
France | La Timone Hospital, Dermatology and cutaneous oncology department | Marseille | |
France | Lapeyronie Hospital, Rheumatology and Immunology department | Montpellier | |
France | Cochin Hospital, Rheumatology department | Paris | |
France | La Pitié-Salpêtrière Hospital, Internal medicine and clinical immunology department | Paris | |
France | Necker Hospital, Adult haematology department | Paris | |
France | Strasbourg Hospital, Rheumatology department | Strasbourg | |
France | Toulouse Hospital, Dermatology department | Toulouse |
Lead Sponsor | Collaborator |
---|---|
Assistance Publique - Hôpitaux de Paris | CEREMAST |
France,
Barete S, Assous N, de Gennes C, Grandpeix C, Feger F, Palmerini F, Dubreuil P, Arock M, Roux C, Launay JM, Fraitag S, Canioni D, Billemont B, Suarez F, Lanternier F, Lortholary O, Hermine O, Frances C. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis. 2010 Oct;69(10):1838-41. doi: 10.1136/ard.2009.124511. Epub 2010 Jun 22. — View Citation
Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11. Erratum In: N Engl J Med. 2009 Nov 5;361(19):1914. — View Citation
Edwards BJ, Bunta AD, Lane J, Odvina C, Rao DS, Raisch DW, McKoy JM, Omar I, Belknap SM, Garg V, Hahr AJ, Samaras AT, Fisher MJ, West DP, Langman CB, Stern PH. Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project. J Bone Joint Surg Am. 2013 Feb 20;95(4):297-307. doi: 10.2106/JBJS.K.01181. — View Citation
Frenzel L, Hermine O. Mast cells and inflammation. Joint Bone Spine. 2013 Mar;80(2):141-5. doi: 10.1016/j.jbspin.2012.08.013. Epub 2012 Oct 30. — View Citation
Johnson MR, Verstovsek S, Jorgensen JL, Manshouri T, Luthra R, Jones DM, Bueso-Ramos CE, Medeiros LJ, Huh YO. Utility of the World Heath Organization classification criteria for the diagnosis of systemic mastocytosis in bone marrow. Mod Pathol. 2009 Jan;22(1):50-7. doi: 10.1038/modpathol.2008.141. Epub 2008 Sep 19. — View Citation
Rabenhorst A, Christopeit B, Leja S, Gerbaulet A, Kleiner S, Forster A, Raap U, Wickenhauser C, Hartmann K. Serum levels of bone cytokines are increased in indolent systemic mastocytosis associated with osteopenia or osteoporosis. J Allergy Clin Immunol. 2013 Nov;132(5):1234-1237.e7. doi: 10.1016/j.jaci.2013.06.019. Epub 2013 Jul 31. No abstract available. — View Citation
Rossini M, Zanotti R, Viapiana O, Tripi G, Idolazzi L, Biondan M, Orsolini G, Bonadonna P, Adami S, Gatti D. Zoledronic acid in osteoporosis secondary to mastocytosis. Am J Med. 2014 Nov;127(11):1127.e1-1127.e4. doi: 10.1016/j.amjmed.2014.06.015. Epub 2014 Jun 20. — View Citation
Theoharides TC, Valent P, Akin C. Mast Cells, Mastocytosis, and Related Disorders. N Engl J Med. 2015 Jul 9;373(2):163-72. doi: 10.1056/NEJMra1409760. No abstract available. — View Citation
van der Veer E, Arends S, van der Hoek S, Versluijs JB, de Monchy JGR, Oude Elberink JNG, van Doormaal JJ. Predictors of new fragility fractures after diagnosis of indolent systemic mastocytosis. J Allergy Clin Immunol. 2014 Dec;134(6):1413-1421. doi: 10.1016/j.jaci.2014.05.003. Epub 2014 Jun 27. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Analysis of the lumbar spine bone mineral density (BMD) | Dual energy x-ray absorptiometry at lumbar spine (L2-L4) | 3 years | |
Secondary | Occurrence of a low energy vertebral fracture and non vertebral fracture | Lateral and front lumbar x-ray | Baseline, 1 year, 2 years and 3 years | |
Secondary | BMD at the total left hip | Dual energy x-ray absorptiometry at lumbar spine (L2-L4) | Baseline, 3 years | |
Secondary | BMD at lumbar spine and the total left hip | Dual energy x-ray absorptiometry at left femoral neck and total left hip | Baseline, 1 year, 2 years | |
Secondary | Biological assays with bone turnover marker of resorption and tryptase levels to assess mastocytosis activity | Withdrawal of 45 ml of blood | Baseline, then every 6 months in 3 years | |
Secondary | Number of serious adverse events to evaluate drug tolerance | Biological assessment: complete blood count, creatinemia, electrolytes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, c-reactive protein (CRP), phosphocalcic analyses with calcemia, phosphoremia, parathormone, vitamin D (25-OH-D), ß-Human Chorionic Gonadotropin (HCG) (if needed)
Clinical assessment: blood pressure, pulse, weight, height, PS, temperature |
Every 6 months in 3 years | |
Secondary | Number of non-serious adverse events to evaluate drug tolerance | Biological assessment: complete blood count, creatinemia, electrolytes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, c-reactive protein (CRP), phosphocalcic analyses with calcemia, phosphoremia, parathormone, vitamin D (25-OH-D), ß-Human Chorionic Gonadotropin (HCG) (if needed)
Clinical assessment: blood pressure, pulse, weight, height, PS, temperature |
Every 6 months in 3 years | |
Secondary | Annual variation of BMD in placebo group and number of low energy fracture compared to historical postmenopausal data | Dual energy x-ray absorptiometry at lumbar spine (L2-L4), left femoral neck and total left hip | Baseline, 1 year, 2 years, 3 years |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT06287502 -
Efficacy of Structured Exercise-Nutritional Intervention on Sarcopenia in Patients With Osteoporosis
|
N/A | |
Completed |
NCT03822078 -
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Denosumab (AMG 162) in Japanese Postmenopausal Women
|
Phase 1 | |
Recruiting |
NCT05845021 -
Surgeon-Initiated Bone Health Referral Pathway in Patients Undergoing Lower Extremity Arthroplasty
|
N/A | |
Completed |
NCT00092066 -
A Study to Evaluate the Safety, Tolerability, and Efficacy of an Investigational Drug and Dietary Supplement in Men and Postmenopausal Women With Osteoporosis (0217A-227)
|
Phase 3 | |
Recruiting |
NCT04754711 -
Interest of Nutritional Care of Children With Sickle Cell Disease on Bone Mineral Density and Body Composition
|
N/A | |
Completed |
NCT04736693 -
Replication of the HORIZON Pivotal Fracture Trial in Healthcare Claims Data
|
||
Not yet recruiting |
NCT06431867 -
Primary Care Management of Osteoporosis in Older Women
|
||
Completed |
NCT02922478 -
Role of Comorbidities in Chronic Heart Failure Study
|
||
Recruiting |
NCT02616627 -
Association Between DXA Results and the Complications, Clinical Courses and Outcomes in Chronic Dialysis Patients
|
||
Recruiting |
NCT02635022 -
Fragility Fracture Liaison Service and Anti-osteoporosis Medication Monitoring Service Study
|
||
Active, not recruiting |
NCT02617303 -
Prevention of Falls and Its Consequences in Elderly People
|
N/A | |
Completed |
NCT02566655 -
Clinical Trial of Intravenous Infusion of Fucosylated Bone Marrow Mesenchyme Cells in Patients With Osteoporosis
|
Phase 1 | |
Completed |
NCT03420716 -
Symbiotic Yogurt, Calcium Absorption and Bone Health in Young Adult Women
|
N/A | |
Not yet recruiting |
NCT02223572 -
Secondary Fracture Prevention in Patients Who Suffered From Osteoporotic Fracture
|
N/A | |
Completed |
NCT02559648 -
Denosumab vs Placebo in Patients With Thalassemia Major and Osteoporosis
|
Phase 2 | |
Unknown status |
NCT01913834 -
Nasally and sc Administered Teriparatide in Healthy Volunteers
|
Phase 1 | |
Not yet recruiting |
NCT01854086 -
Compliance and Persistence With Osteoporosis Treatment and Attitude Towards Future Therapy Among Post-menopausal Israeli Women During Drug Treatment or Drug Holiday
|
N/A | |
Completed |
NCT02003716 -
DeFRA Questionnaire as an Anamnestic Form
|
N/A | |
Completed |
NCT02143674 -
Muscle Strengthening Exercises and Global Stretching in Elderly
|
N/A | |
Completed |
NCT01694784 -
Understanding and Discouraging Overuse of Potentially Harmful Screening Tests
|
N/A |