Ignite Creation Date:
2024-05-06 @ 1:50 AM
Last Modification Date:
2024-10-26 @ 11:10 AM
Study NCT ID:
NCT01916317
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-11-22
First Post:
2013-08-01
Brief Title:
Randomized Controlled Trial to Assess Blockade of Voltage Gated Sodium Channels During Surgery in Operable Breast Cancer
Sponsor:
Tata Memorial Hospital
Organization:
Tata Memorial Hospital
Study Overview
Official Title:
Randomized Controlled Trial to Assess Blockade of Voltage Gated Sodium Channels During Surgery in Operable Breast Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Voltage Gated Sodium Channels Over the years there is more evidence that ionic channels are involved in the oncogenic process Among these voltage gated sodium channels VGSC expressed in non-nervous or non-muscular organs are often associated with the metastatic behavior of different cancers
Expression of VGSCs has been reported both in vitro andor in vivo in a range of human carcinomas including breast cancer Ion channels are major signaling molecules expressed in a wide variety of tissues They are involved in determining a variety of cellular functions like proliferation solute transport volume control enzyme activity secretion invasion gene-expression excitation-contraction coupling and intercellular communication4 VGSC activity contributes to much cellular behavior integral to metastasis including cellular process extension lateral motility and galvanotaxis transverse invasion and secretory membrane activity
A correlation between Na transport and oncogenesis has been widely reported in literature In 1980 transformed mouse mammary cells were shown to have 3-fold higher intra-cellular sodium content than untransformed cells5 Additionally evidence suggest that increasing the inward sodium current through voltage gated sodium channels increased the invasive capacity of breast cancer6 Also growth and proliferation of mammary adenocarcinoma cells can be inhibited by Amiloride suggesting that epithelial Na channels ENaC activity is correlated with proliferation of breast cancer cells
Current evidence suggests that VGSC activity is necessary and sufficient for cancer cell invasiveness8 A recent in vitro study has shown that the human MDA MB 231 breast cancer cell line expressed functional VGSCs9 However the molecular nature of the VGSC and its functional relevance to breast cancer in vivo are currently under study
Surgical operations for cancer have been reported to induce dissemination of cancer cells into surrounding tissues or into the circulation1011and infiltration anesthetics can inhibit immune response12-14 Although the mechanism remains to be elucidated infiltration anesthetics such as lidocaine have membrane- stabilizing action Seeman 1972 and these agents could have direct effects on cancer cells Therefore it is important to clarify the effects of infiltration anesthetics on behavior of the tumor cells
Commonly used local anesthetic agents inhibit the VGSCs and also possess a unique membrane stabilizing action through other unknown mechanisms A study by Mammota et al 15 reported that lignocaine effectively inhibited the invasive ability of human cancer HT1080 HOS and RPMI-7951 cells at concentrations used in surgical operations 5-20 mM Lidocaine reduced the invasion ability of these cells by partly inhibiting the shedding of HB-EGF from the cell surface and modulation of intracellular Ca2 concentration contributed to this action In addition lidocaine 5-30 mM infiltrated around the inoculation site inhibited pulmonary metastases of murine osteosarcoma LM 8 cells in vivo
Dose of lidocaine15
40 mM 1 lidocaine is usually used for infiltration anesthesia for surgical operations Lower concentrations 1-20mM of lidocaine were sufficient to suppress the invasive ability of cancer cells14 One mM lidocaine inhibited the invasive ability of HT1080 cells by about 50 and 20 mM lidocaine inhibited the invasion ability completely Lidocaine also inhibited dose-dependently the invasive ability of HOS and RPMI-7951 cells although it was less effective on HOS cells Lignocaine exerts its anesthetic action by obstructing the sodium channel 16 however 10 mMof tetrodotoxin TTX a specific sodium channel inhibitor had little effect on the invasive ability of HT1080 cells Ten mM lidocaine-N-ethylbromide NEB which does not cross the cell membrane also had little effect on the invasive ability of the cells
Objectives
Primary Objective
To assess the in-vivo ability of local anesthetics agents like lignocaine to decrease the dissemination of cancer cells during surgery and improve the disease free interval
Secondary Objective
To assess the in-vivo ability of local anesthetics agents like lignocaine on impacting long term survival
Methodology Treatment plan
The study drug 05 lidocaine 60mM will be tested in the intraoperative setting prior to surgery will be tested in a randomized setting
Arm A 60mM of 05 lignocaine will be injected peritumoral prior to excision The local anesthetic should be injected on all 6 surfaces of the tumor and also within the tumor Wait for 7 minutes for its action followed by surgery Intervention arm Arm B No injection of lignocaine prior to excision Control arm
Expression of VGSCs has been reported both in vitro andor in vivo in a range of human carcinomas including breast cancer Ion channels are major signaling molecules expressed in a wide variety of tissues They are involved in determining a variety of cellular functions like proliferation solute transport volume control enzyme activity secretion invasion gene-expression excitation-contraction coupling and intercellular communication4 VGSC activity contributes to much cellular behavior integral to metastasis including cellular process extension lateral motility and galvanotaxis transverse invasion and secretory membrane activity
A correlation between Na transport and oncogenesis has been widely reported in literature In 1980 transformed mouse mammary cells were shown to have 3-fold higher intra-cellular sodium content than untransformed cells5 Additionally evidence suggest that increasing the inward sodium current through voltage gated sodium channels increased the invasive capacity of breast cancer6 Also growth and proliferation of mammary adenocarcinoma cells can be inhibited by Amiloride suggesting that epithelial Na channels ENaC activity is correlated with proliferation of breast cancer cells
Current evidence suggests that VGSC activity is necessary and sufficient for cancer cell invasiveness8 A recent in vitro study has shown that the human MDA MB 231 breast cancer cell line expressed functional VGSCs9 However the molecular nature of the VGSC and its functional relevance to breast cancer in vivo are currently under study
Surgical operations for cancer have been reported to induce dissemination of cancer cells into surrounding tissues or into the circulation1011and infiltration anesthetics can inhibit immune response12-14 Although the mechanism remains to be elucidated infiltration anesthetics such as lidocaine have membrane- stabilizing action Seeman 1972 and these agents could have direct effects on cancer cells Therefore it is important to clarify the effects of infiltration anesthetics on behavior of the tumor cells
Commonly used local anesthetic agents inhibit the VGSCs and also possess a unique membrane stabilizing action through other unknown mechanisms A study by Mammota et al 15 reported that lignocaine effectively inhibited the invasive ability of human cancer HT1080 HOS and RPMI-7951 cells at concentrations used in surgical operations 5-20 mM Lidocaine reduced the invasion ability of these cells by partly inhibiting the shedding of HB-EGF from the cell surface and modulation of intracellular Ca2 concentration contributed to this action In addition lidocaine 5-30 mM infiltrated around the inoculation site inhibited pulmonary metastases of murine osteosarcoma LM 8 cells in vivo
Dose of lidocaine15
40 mM 1 lidocaine is usually used for infiltration anesthesia for surgical operations Lower concentrations 1-20mM of lidocaine were sufficient to suppress the invasive ability of cancer cells14 One mM lidocaine inhibited the invasive ability of HT1080 cells by about 50 and 20 mM lidocaine inhibited the invasion ability completely Lidocaine also inhibited dose-dependently the invasive ability of HOS and RPMI-7951 cells although it was less effective on HOS cells Lignocaine exerts its anesthetic action by obstructing the sodium channel 16 however 10 mMof tetrodotoxin TTX a specific sodium channel inhibitor had little effect on the invasive ability of HT1080 cells Ten mM lidocaine-N-ethylbromide NEB which does not cross the cell membrane also had little effect on the invasive ability of the cells
Objectives
Primary Objective
To assess the in-vivo ability of local anesthetics agents like lignocaine to decrease the dissemination of cancer cells during surgery and improve the disease free interval
Secondary Objective
To assess the in-vivo ability of local anesthetics agents like lignocaine on impacting long term survival
Methodology Treatment plan
The study drug 05 lidocaine 60mM will be tested in the intraoperative setting prior to surgery will be tested in a randomized setting
Arm A 60mM of 05 lignocaine will be injected peritumoral prior to excision The local anesthetic should be injected on all 6 surfaces of the tumor and also within the tumor Wait for 7 minutes for its action followed by surgery Intervention arm Arm B No injection of lignocaine prior to excision Control arm
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None