Radiation is commonly used to treat cancer in the head and neck, however, this can lead to a serious complication called osteoradionecrosis (ORN), where there is necrotic (dead) open bone inside or outside of the mouth. This complication is difficult to treat, involves large healthcare costs, and can have devastating effects on quality of life.
Two common adjuncts used in treatment of ORN are hyperbaric oxygen therapy (HBOT), which may requires up to 60 treatments at a specialized clinic where patients are treated with high concentrations of oxygen using special chambers, and a less complex option called PENTOCLO which involves treating patients with several antibiotics followed by a combination of other oral medications taken for at least 1 year.
This pilot study will be guide the design of a definitive trial to examine if the combination of HBOT and a modified PENTOCLO protocol together is better than the current standard treatment of HBOT alone. Outcomes will include pain, side effects and the need for surgery in patients with ORN. Specifically, the results of this small, pilot study will help to inform the design of a future larger study.

Start Date01 May 2024

Sponsor / Collaborator

Sunnybrook Health Sciences Centre

NCT06263517 / RecruitingPhase 2/3

Adaptative, Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled, Clinical Trial, on the Efficacy and Tolerability of Different Escalating Doses of Intra-articular Clodronate in Patients With Painful Knee Osteoarthritis

The goal of this clinical trial is to to clarify which is the best dose of administration, to select a dose and to confirm the therapeutic efficacy of clodronate in patients with painful knee osteoarthritis (OA). The clinical trial will be divided in two parts.
The main questions it aims to answer are:
in Phase II, to assess the safety and tolerability of different escalating doses of intra articular (IA) clodronate
in Phase II, to set a defined therapeutic dose (DTD) to be used in Phase III
in Phase III, to assess the safety and tolerability of different escalating doses of IA clodronate to confirm and extensively evaluate the therapeutic efficacy and safety of the clodronate DTD in patients with knee OA

Start Date12 Oct 2023

Sponsor / Collaborator

Società Prodotti Antibiotici SpA

[+1]

EUCTR2021-003124-33-IT / Unknown statusPhase 2/3

Adaptative, multicenter, randomized, double-blind, parallel-group, placebo controlled, clinical trial, on the efficacy and tolerability of different escalating doses of intra-articular clodronate in patients with painful knee osteoarthritis - SPA-S-899-01-21

Start Date15 May 2023

Sponsor / Collaborator-

100 Clinical Results associated with Clodronate Disodium

100 Translational Medicine associated with Clodronate Disodium

100 Patents (Medical) associated with Clodronate Disodium

2,525

Literatures (Medical) associated with Clodronate Disodium

01 Dec 2024·Molecular biology reports

Mycobacterium marinum mediates regulation of prostaglandin E2 expression on host immune response through cyclooxygenase pathway

Article

Author: Xu, Cheng ; Zhou, Lei ; Chen, Zhenhua ; Mo, Liyi ; Lin, Bingyao ; Luo, Yanwen ; Lin, Dongzi ; Tian, Honghong ; Wang, Xuezhi

PURPOSE:

Investigate the role of COX signaling in activating the PGE2-EP2 pathway.

METHODS:

Utilized a marine Mycobacterium infection model in zebrafish. Marine mycobacteria were stained with fluorescein isothiocyanate. The COX inhibitor indomethacin, EP2 receptor inhibitor AH6809, EP4 receptor inhibitor AH23848 and clodronate Liposomes were used to investigate the role of COX, EP2, EP4 and macrophage whether participating in combat marine mycobacterial infection. The expression level of the target gene was detected using real-time fluorescence quantitative PCR instrument.

RESULTS:

The findings revealed that larvae exposed to the COX inhibitor indomethacin or the EP2 receptor inhibitor AH6809 demonstrated a significantly higher mortality rate due to marine mycobacterium infection than those in the control group. Administration of exogenous prostaglandin E2 (PGE2) rescued the survival of zebrafish infected with marine mycobacteria and treated with indomethacin. Additionally, a significant reduction in survival rate was noted in macrophage-depleted zebrafish infected with marine mycobacteria.

CONCLUSION:

The host may combat marine mycobacterium infection via COX signaling, which activates the PGE2-EP2 pathway and mediates macrophage resistance.

01 Feb 2024·The American journal of pathology

Macrophage Activation in Synovitis and Osteoarthritis of Temporomandibular Joint and Its Relationship with the Progression of Synovitis and Bone Remodeling

Article

Author: Liu, Xin ; Li, Huimin ; Hu, Shiyu ; Long, Xing ; Ke, Jin ; Jiang, Henghua

This study investigates the regulatory mechanisms of synovial macrophages and their polarization in the progression of temporomandibular joint osteoarthritis (TMJOA). Macrophage depletion models were established by intra-articular injection of clodronate liposomes and unloaded liposomes. TMJOA was induced by intra-articular injection of 50 μL Complete Freund's Adjuvant and the surgery of disc perforation. The contralateral joint was used as the control group. The expression of F4/80, CD86, and CD206 in the synovium was detected by immunofluorescence staining analysis. Hematoxylin and eosin staining and TMJOA synovial score were detected to show the synovial changes in rat joints after TMJOA induction and macrophage depletion. Changes in rat cartilage after TMJOA induction and macrophage depletion were shown by safranin fast green staining. The bone-related parameters of rats' joints were evaluated by micro-computed tomography analysis. The TMJOA model induced by Complete Freund's Adjuvant injection and disc perforation aggravated synovial hyperplasia and showed a significant up-regulation of expression of F4/80-, CD86-, and CD206-positive cells. F4/80, CD86, and CD206 staining levels were significantly decreased in macrophage depletion rats, whereas the synovitis score further increased and cartilage and subchondral bone destruction was slightly aggravated. Macrophages were crucially involved in the progression of TMJOA, and macrophage depletion in TMJOA synoviocytes promoted synovitis and cartilage destruction.

15 Jan 2024·FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Recruitment of large peritoneal macrophages to capsular fibrosis developed on the liver surface

Article

Author: Jeong, Soi ; Balog, Steven ; Asahina, Kinji

Abstract:

Upon injury to Glisson's capsule, mesothelial cells covering the liver surface differentiate into myofibroblasts and participate in capsular fibrosis. In the fibrotic area, infiltrating macrophages are present, but their origin and role in capsular fibrosis remain elusive. In the present study, we examined whether macrophages in the peritoneal cavity migrate to the liver and participate in capsular fibrosis. Capsular fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. Chlorhexidine gluconate treatment induced disappearance of CD11bHigh F4/80High large peritoneal macrophages from the peritoneal cavity. Transplantation of TIMD4+ large peritoneal macrophages to the mouse peritoneal cavity resulted in their recruitment to the fibrotic area of the liver. Bone marrow‐derived monocytes were also recruited to the chlorhexidine gluconate‐induced fibrotic area upon their transplantation to the peritoneal cavity. However, bone marrow‐derived macrophages, Kupffer cells, peritoneal B cells, and small peritoneal macrophages prepared from chlorhexidine gluconate‐treated mice did not exhibit such potential. In the hepatic fibrotic area, peritoneal macrophages lost expression of unique markers (Gata6, Timd4) and increased expression of genes involved in inflammation (Il1b, Il6, Tnf) and extracellular matrix remodeling (Mmp13, Timp1). Depletion of peritoneal macrophages by clodronate liposomes reduced capsular fibrosis. Our data indicate that large peritoneal macrophages are recruited to the injured liver surface and promote capsular fibrosis by inducing inflammation and extracellular matrix remodeling. Modulating the function of peritoneal macrophages might be a new approach for suppressing capsular fibrosis.

News (Medical) associated with Clodronate Disodium

30 May 2023

·www.pharmaceutical-technology.com

Abiogen acquires EffRx to fortify bone disease portfolio

Akosua Mireku @AkosuaMireku1 A man sitting on living room sofa holding his painful shoulder. Abiogen develops drugs for osteoarthritis. Credit: RealPeopleGroup via Getty Images The Italian pharmaceutical company Abiogen Pharma completed an acquisition of a 97.09% stake in the Swiss orphan conditions-focused EffRx Pharmaceuticals on May 29. This deal follows Abiogen’s recent acquisition of the Cologne, Germany-based Altamedics in December 2022. Altamedics specialises in pharmaceutical distribution in hospital settings. The €8 million ($8,559,480) deal was Abiogen’s first move in its global expansion plan and the deal with EffRx is a continuation of this. Abiogen Pharma specialises in osteoarticular and bone metabolism diseases amongst other therapy areas. The company has developed three bisphosphonates, clodronate, alendronate and Nerixia (neridronate), for the treatment of bone pathologies such as osteoarthritis . Bisphosphonates are drugs that slow the progression of bone loss. EffRx has received several European regulatory approvals for drugs in its portfolio . For example, in July 2022, EffRx launched its paediatric adrenal insufficiency replacement therapy Alkindi (hydrocortisone) in Switzerland. Alkindi is one of EffRx’s three marketed drugs. The company developed and launched Binosto (alendronate sodium) as the first and only buffered solution for osteoporosis. The European Medicines Agency has also approved Efmody for the treatment of congenital adrenal hyperplasia medicine in patients ages 12 years and above in the European Union. The company’s last deal included an exclusive license agreement with the Cardiff, UK-headquartered specialty pharmaceuticals company Diurnal group for the commercialisation of Efmody (hydrocortisone) in Switzerland. In Italy, Abiogen began distributing its bisphosphonates in 2014 and has since seen some successful drug approvals. The biotech transferred the rights for alendronate to Merck which marketed the drug under the brand name Vancapsi. The Italian health authorities also gave Abiogen’s Nerixia the country’s first rare disease designation for Osteogenesis Imperfecta and Complex regional pain syndrome, for which the drug is now approved in Italy. Separate from drug development, the Italian company also offers contract manufacturing and clinical supply services. In a press release , Abiogen’s International Business Unit Head, Prisca Di Martino said, “We are working towards developing Abiogen into an international business, without losing sight of our nature as an Italian and family-run undertaking, and we are pursuing this target by entering into agreements with foreign businesses that share our goals and therapeutic areas.”

Drug ApprovalAcquisitionLicense out/in

14 Jul 2022

·www.prnewswire.com

Study shows that selection of breast cancer patients for adjuvant bisphosphonate therapy based on Inbiomotion's MAFTEST® reduces the risk of death in comparison with current clinical guidance

MAFTEST® analyses of the NSABP-B34 and AZURE landmark clinical trials confirmed clinical utility of the MAFTEST® for selection of early-stage breast cancer patients that benefit from adjuvant clodronate treatment. Reduces the risk of death at 5 and 10 years by 26% and 23% respectively. Identifies almost twice as many patients able to benefit from the intervention than are selected using current clinical guidelines. Data published in Annals of Oncology, (33), SUPPLEMENT 3, S152, 2022. BARCELONA, Spain, July 14, 2022 /PRNewswire/ -- Inbiomotion SL, a company developing a unique single-gene-based biomarker for the personalized adjuvant treatment of early-stage (stage I-III) breast cancer patients, announces the results of comparing the clinical efficacy of implementing the proprietary MAFTEST® for selection of patients for adjuvant bisphosphonates therapy with current clinical guidance. The results were presented at the ESMO 2022 Breast Cancer Symposium. The data show that stratification of early breast cancer patients according to MAF status reduced the risk of death and relapse in MAF negative patients by 26% and 23% respectively, compared to a 12% and 15% reduction in the risk of death or relapse seen with stratification by menopausal status recommended by current ESMO and ASCO Clinical Guidelines. The data also indicate that adjuvant treatment with bisphosphonates should be avoided in MAF positive patients as the risk of death and relapse is increased 16% and 15% respectively in these patients. In addition, the study shows that the use of MAF status for selection of early breast cancer patients for treatment with bisphosphonates allows the treatment of young premenopausal patients currently excluded by existing clinical guidance. "The MAF biomarker allows a new paradigm for selection of patients for adjuvant bisphosphonate treatment of early breast cancer that not only identifies those patients that will benefit from treatment (MAF negatives) but also excludes patients that could be harmed (MAF positives). This new selection criteria not only reduces the risk of death and relapse for selected patients but also provides a new treatment option for young patients currently excluded from this treatment in current clinical practice," said Robert Coleman, Professor Emeritus, Department of Oncology and Metabolism, University of Sheffield, UK. Currently, clodronate and other bisphosphonates are not approved by the regulatory agencies for use in adjuvant treatment of the broad population of early-stage breast cancer patients. However, they are recommended in the ASCO/CCO and ESMO clinical guidelines for adjuvant treatment of breast cancer in postmenopausal patients. The study shows that identifying MAF-negative patients for selection for adjuvant treatment with bisphosphonates outperforms current selection by menopausal status and could give more patients, particularly younger patients, the opportunity to benefit from adjuvant bisphosphonates, while avoiding potential harm (or no benefit), than solely using menopausal status as a selection criterion. "Our results indicate that adjuvant clodronate treatment has a large clinical benefit if restricted to MAF-negative patients," said Prof. Alexander Paterson, principal investigator of the NSABP-B34 clinical trial and Emeritus Clinical Professor at the Department of Oncology, University of Calgary. "Our data provide an objective criterion for patient selection for bisphosphonate adjuvant treatment that outperforms current selection based on menopausal status." "This study confirms our previous findings and the clinical utility of MAFTEST® as a unique tool for precision medicine in early breast cancer. Every year approximately 355,000 women are diagnosed with early breast cancer in Europe with a 10% risk of death at 5 years. Using MAF Test these deaths could be reduced by 26%, which would translate to 9,230 lives saved," said Joël Jean-Mairet, Executive Chairman of the Board of Inbiomotion. "We have discovered and developed a new biomarker, MAF gene amplification, that if used as selection criteria for adjuvant treatment with bisphosphonates improves the clinical outcome of breast cancer patients compared with current clinical practice, " said Prof. Roger Gomis, ICREA Research Professor at IRB Barcelona. "MAF Test is a biomarker that is easy to implement in any clinical pathology lab and should be considered for routine characterization of breast cancer tumors." Recently the MAFTEST® obtained the CE-mark as an in vitro diagnostic medical device for prognostic purposes. Since clodronate and other bisphosphonates are not approved by the regulatory agencies for use in adjuvant treatment of early-stage breast cancer patients, Inbiomotion's MAFTEST® is not authorized to be used as a companion diagnostic as described in the above-mentioned study. Reference articles: Impact of MAF selection of patients for adjuvant bisphosphonate therapy and comparison with current clinical guidance Robert Coleman, Roger R Gomis, Alexander H G Paterson. Full text article : (22)00461-6/fulltext MAF amplification and adjuvant clodronate outcomes in early-stage breast cancer in NSABP B-34 and potential impact on clinical practice Alexander H G Paterson et al. Full text article: Effect of MAF amplification on treatment outcomes with adjuvant zoledronic acid in early breast cancer: a secondary analysis of international, open-label, randomized, controlled, phase 3 AZURE (BIG 01/04) trial Robert Coleman et al. Full text article: (17)30603-4/fulltext Benefits and risks of adjuvant treatment with zoledronic acid in stage II/III breast cancer. 10 years follow-up of the AZURE randomized clinical trial (BIG 01/04) Robert Coleman et al. Full text article: About Inbiomotion: Inbiomotion SL, a company founded by Prof. Roger Gomis, is developing a unique single gene-based biomarker for the personalized adjuvant treatment of early-stage breast cancer patients. The biomarker has been technically and analytically validated. The results of the first trial using well annotated archived specimens of the AZURE registrational clinical trial, now confirmed in the NSABP-B34 trial, indicate its potential use as a companion diagnostic. The company holds over 200 patents and patent applications covering its proprietary FISH MAFTEST® and the use of bisphosphonates in the adjuvant treatment of early-stage breast cancer patients. About MAF: MAF (mesenchymal aponeurotic fibrosarcoma gene, an AP-1 family transcription factor) is expressed in primary cancer tumors. This is associated with increased metastasis, especially bone metastasis. MAF transcriptionally controls genes such PTHrP, which regulate metastasis-related cellular processes, including survival, initiation, metabolic rewiring, and particularly, adhesion to bone marrow–derived cells and osteoclast differentiation. These observations point to MAF having a key hierarchical role in metastasis. SOURCE Inbiomotion

ASCO

100 Deals associated with Clodronate Disodium

External Link

KEGG	Wiki	ATC	Drug Bank
D03544	Clodronate Disodium	M05BA02	DB00720

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Bone metastases	FR	-	27 Nov 1994
Humoral Hypercalcemia of Malignancy	CA	Bayer, Inc.	31 Dec 1992
Bone Diseases	-	-	01 Jan 1986
Hypercalcemia	-	-	01 Jan 1986
Osteoporosis	-	-	01 Jan 1986

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Osteoarthritis	Phase 3	IT	Abiogen Pharma SpA	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASGCT2023	Not Applicable	-	-	Clodronate liposomes	frpmuchjyd(qffnxnnvui) = tgxdrboxot egdsvybsbx (liwcptkxmc )	-	01 May 2023
				Control (no clodronate pre-treatment)	frpmuchjyd(qffnxnnvui) = tuqqwtabqu egdsvybsbx (liwcptkxmc )
EULAR2010	Not Applicable	Osteoarthritis, Knee	122	Clodronate i.v. 300mg/die	baszmqnpwh(cpapgupstm) = osktjnisvz jbxhbuhcjm (bckaiyacup )	-	16 Jun 2010
MRC PR04 and PR05 (Pubmed \| Lancet Oncol)	Not Applicable	Prostatic cancer metastatic Adjuvant	-	Sodium clodronate	rtveknvyuu(chxcyfettn): HR = 0.77 (95% CI, 0.6 - 0.98), P-Value = 0.032	Positive	01 Sep 2009
				Placebo
ASCO2007	Phase 3	Bone metastases	46	Oral Clodronate	ytdjgulvdh(jzwmgkhgoi) = viqgpvpobv zijyftslsf (gboyzuhljo ) View more	-	20 Jun 2007
				Oral Ibandronate	ytdjgulvdh(jzwmgkhgoi) = yxnwbtmsdu zijyftslsf (gboyzuhljo ) View more
ASCO2006	Not Applicable	Early Stage Breast Carcinoma Adjuvant	268	Clodronate	jjswonkyoz(dpaixoggfj) = xgjgqzbkiz jtgpcphaqg (zpyjwnkejq ) View more	-	20 Jun 2006
ASCO2005	Not Applicable	Breast Cancer	1,069	Oral clodronate 1600mg	zqilghogmu(hqoximtcxu) = yeujjqdgtc mikskryaff (miwdxcipmw, 0.010–0.021)	-	01 Jun 2005
ASCO2004	Not Applicable	Node-positive breast cancer Adjuvant	299	Clodronate 1600 mg daily	ootvdmijth(xlbrdkzhjj) = vvsnrvlega sfnyldetyw (gfxogzjsos ) View more	Negative	15 Jul 2004
				clodronate (Control)	ootvdmijth(xlbrdkzhjj) = vlydksmqih sfnyldetyw (gfxogzjsos ) View more
NCT00009945 (Pubmed \| Drug Saf)	Phase 3	Breast Cancer Adjuvant	1,079	Oral clodronate 1600 mg/day	msvnqthrky(panltfwcgg) = ojrkulppzl pkhtinimvj (vcftbkgphl ) View more	-	01 Jan 2003
				Placebo	msvnqthrky(panltfwcgg) = sjketakher pkhtinimvj (vcftbkgphl, 4.0 - 15.6) View more
NCT00009945 (Pubmed \| J Urol)	Phase 3	Breast Cancer	3,323	Clodronate 1,600 mg/d	uvvxxdkgij(lertiborlc): HR = 0.77 (95% CI, 0.56 - 1.08)	Positive	01 Aug 2002
				Placebo

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