scholarly journals First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot trial 1

2019 ◽  
Vol 130 (2) ◽  
pp. 476-485 ◽  
Author(s):  
Michael A. Vogelbaum ◽  
Cathy Brewer ◽  
Gene H. Barnett ◽  
Alireza M. Mohammadi ◽  
David M. Peereboom ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Pilot Trial ◽  
Drug Application ◽  
Volume Of Distribution ◽  
High Grade ◽  
Drug Infusion ◽  
Clinical Trial Registration ◽  
Gadolinium Dtpa ◽  
Stereotactic Technique ◽  
The Brain

OBJECTIVEProgress in management of high-grade gliomas (HGGs) has been hampered by poor access of potential therapeutics to the CNS. The Cleveland Multiport Catheter (CMC), which deploys 4 independent delivery microcatheters, was developed to be a reliable, high-volume delivery device for delivery of therapeutic agents to the brain and other solid organs. The authors undertook this first-in-human clinical trial effort to evaluate the delivery characteristics of the CMC in patients with HGGs.METHODSA series of pilot studies were launched after approval of a sponsor-investigator IND (investigational new drug) application to evaluate the delivery of topotecan and gadolinium-DTPA (Gd-DTPA) via the CMC in patients with recurrent HGG. The first pilot trial evaluated delivery into enhancing tumor and nonenhancing, tumor-infiltrated brain. Two catheters were placed with the use of a conventional frameless stereotactic technique following a biopsy to confirm tumor recurrence, and drug infusion was performed both intraoperatively and postoperatively for a total of 96 hours with the same rate for all microcatheters. Delivery was assessed by intermittent MRI.RESULTSThree patients were enrolled in the first pilot study. MRI demonstrated delivery from all 6 catheters (24 microcatheters). The volume of distribution (Vd) of Gd-DTPA was heavily dependent upon CMC location (enhancing vs nonenhancing) with an approximately 10-fold difference in Vd observed (p = 0.005). There were no hemorrhages related to catheter placement or removal, and all 3 patients completed the protocol-defined treatment.CONCLUSIONSThe CMC is capable of providing backflow-resistant drug delivery to the brain and brain tumors. The volume of distribution is heavily dependent upon the integrity of the blood-brain barrier. Assessment of delivery is essential for development of loco-regionally applied therapeutics in the CNS.Clinical trial registration no.: NCT02278510 (clinicaltrials.gov)

scholarly journals A Phase 2 Randomised Clinical Trial Assessing the Tolerability of Two Different Ratios of Medicinal Cannabis in Patients With High Grade Gliomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Janet Schloss ◽  
Judith Lacey ◽  
Justin Sinclair ◽  
Amie Steel ◽  
Michael Sughrue ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Grade Glioma ◽  
Randomised Clinical Trial ◽  
Trial Registration ◽  
Brain Morphology ◽  
Control Group ◽  
High Grade ◽  
Serious Adverse Events ◽  
Clinical Trial Registration ◽  
Medicinal Cannabis

BackgroundCannabis for cancer is very topical and, given the use of illicit cannabis preparations used in this vulnerable population, research investigating standardised, quality-assured medicinal cannabis is critical to inform clinicians and assist patient safety.MethodsA randomized trial involving adult patients diagnosed with a high-grade glioma, no history of substance abuse, liver or kidney damage or myocardial infarction were eligible for inclusion in a tolerability study on two different ratios of medicinal cannabis. Baseline screening of brain morphology, blood pathology, functional status, and cognition was conducted. A retrospective control group was used for comparison for secondary outcomes.ResultsParticipants (n=88) were on average 53.3 years old. A paired t-test assessed the Functional Assessment of Cancer Therapy for Brain Cancer (FACT-Br) between groups from baseline to week 12 found that the 1:1 ratio favoured both physical (p=0.025) and functional (p=0.014) capacity and improved sleep (p=0.009). Analysis of changes from baseline to week 12 also found 11% of 61 participants had a reduction in disease, 34% were stable, 16% had slight enhancement, and 10% had progressive disease. No serious adverse events occurred. Side effects included dry mouth, tiredness at night, dizziness, drowsiness.ConclusionThis study demonstrated that a single nightly dose of THC-containing medicinal cannabis was safe, had no serious adverse effects and was well tolerated in patients. Medicinal cannabis significantly improved sleep, functional wellbeing, and quality of life.Clinical Trial RegistrationAustralian New Zealand Clinical Trials Registry (ANZCTR) http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373556&isReview=true, identifier ACTRN12617001287325.

scholarly journals Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 40
Author(s):  
Chibueze D. Nwagwu ◽  
Amanda V. Immidisetti ◽  
Gabriela Bukanowska ◽  
Michael A. Vogelbaum ◽  
Anne-Marie Carbonell
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Real Time ◽  
Study Design ◽  
Tumor Resection ◽  
Drug Application ◽  
Phase I Clinical Trial ◽  
Β1 Integrin ◽  
High Grade ◽  
Convection Enhanced Delivery

Introduction: OS2966 is a first-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for the intratumoral, convection-enhanced delivery (CED) of OS2966. Gadolinium contrast will be added to OS2966 before each infusion, enabling the real-time visualization of therapeutic distribution via MRI. Subsequently, patients will undergo their clinically indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: (1) the latest CED technology, (2) 2-part design including neoadjuvant intratumoral administration, (3) a first-in-class investigational therapeutic, and (4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active.

scholarly journals Spreading depolarization in acute brain injury inhibited by ketamine: a prospective, randomized, multiple crossover trial

2019 ◽  
Vol 130 (5) ◽  
pp. 1513-1519 ◽  
Author(s):  
Andrew P. Carlson ◽  
Mohammad Abbas ◽  
Robert L. Alunday ◽  
Fares Qeadan ◽  
C. William Shuttleworth
Keyword(s):  
Clinical Trial ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Pilot Trial ◽  
Clinical Intervention ◽  
Controlled Clinical Trial ◽  
Clinical Trial Registration ◽  
Spreading Depolarization ◽  
Increased Risk ◽  
Wide Range

OBJECTIVERetrospective clinical data and case studies support a therapeutic effect of ketamine in suppression of spreading depolarization (SD) following brain injury. Preclinical data strongly support efficacy in terms of frequency of SD as well as recovery from electrocorticography (ECoG) depression. The authors present the results of the first prospective controlled clinical trial testing the role of ketamine used for clinical sedation on occurrence of SD.METHODSTen patients with severe traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH) were recruited for this pilot trial. A standard ECoG strip was placed at the time of craniotomy, and the patients were then placed on an alternating every-6-hour schedule of ketamine or other sedation agent. The order of treatment was randomized. The ketamine dose was adjusted to clinical effect or maintained at a subanesthetic basal dose (0.1 mg/kg/hr) if no sedation was required. SD was scored using standard criteria, blinded to ketamine dosing. Occurrence of SD was compared with the hourly dose of ketamine to determine the effect of ketamine on SD occurrence.RESULTSSuccessful ECoG recordings were obtained in all 10 patients: 8 with SAH and 2 with TBI. There were a total of 1642 hours of observations with adequate ECoG: 833 hours off ketamine and 809 hours on ketamine. Analysis revealed a strong dose-dependent effect such that hours off ketamine or on doses of less than 1.15 mg/kg/hr were associated with an increased risk of SD compared with hours on doses of 1.15 mg/kg/hr or more (OR 13.838, 95% CI 1.99–1000). This odds ratio decreased with lower doses of 1.0 mg/kg/hr (OR 4.924, 95% CI 1.337–43.516), 0.85 mg/kg/hr (OR 3.323, 95% CI 1.139–16.074), and 0.70 mg/kg/hr (OR 2.725, 95% CI 1.068–9.898) to a threshold of no effect at 0.55 mg/kg/hr (OR 1.043, 95% CI 0.565–2.135). When all ketamine data were pooled (i.e., on ketamine at any dose vs off ketamine), a nonsignificant overall trend toward less SD during hours on ketamine (χ2 = 3.86, p = 0.42) was observed.CONCLUSIONSKetamine effectively inhibits SD over a wide range of doses commonly used for sedation, even in nonintubated patients. These data also provide the first prospective evidence that the occurrence of SD can be influenced by clinical intervention and does not simply represent an unavoidable epiphenomenon after injury. These data provide the basis for future studies assessing clinical improvement with SD-directed therapy.Clinical trial registration no.: NCT02501941 (clinicaltrials.gov)

scholarly journals Effect of noisy galvanic vestibular stimulation on dynamic posture sway under visual deprivation in patients with bilateral vestibular hypofunction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Po-Yin Chen ◽  
Ying-Chun Jheng ◽  
Chien-Chih Wang ◽  
Shih-En Huang ◽  
Ting-Hua Yang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Light Exposure ◽  
Light Condition ◽  
Vestibular Stimulation ◽  
Galvanic Vestibular Stimulation ◽  
Lateral Deviation ◽  
Clinical Trial Registration ◽  
Vestibular Hypofunction ◽  
Dark Conditions ◽  
Bilateral Vestibular Hypofunction

AbstractA single-blind study to investigate the effects of noisy galvanic vestibular stimulation (nGVS) in straight walking and 2 Hz head yaw walking for healthy and bilateral vestibular hypofunction (BVH) participants in light and dark conditions. The optimal stimulation intensity for each participant was determined by calculating standing stability on a force plate while randomly applying six graded nGVS intensities (0–1000 µA). The chest–pelvic (C/P) ratio and lateral deviation of the center of mass (COM) were measured by motion capture during straight and 2 Hz head yaw walking in light and dark conditions. Participants were blinded to nGVS served randomly and imperceivably. Ten BVH patients and 16 healthy participants completed all trials. In the light condition, the COM lateral deviation significantly decreased only in straight walking (p = 0.037) with nGVS for the BVH. In the dark condition, both healthy (p = 0.026) and BVH (p = 0.017) exhibited decreased lateral deviation during nGVS. The C/P ratio decreased significantly in BVH for 2 Hz head yaw walking with nGVS (p = 0.005) in light conditions. This study demonstrated that nGVS effectively reduced walking deviations, especially in visual deprived condition for the BVH. Applying nGVS with different head rotation frequencies and light exposure levels may accelerate the rehabilitation process for patients with BVH.Clinical Trial Registration This clinical trial was prospectively registered at www.clinicaltrials.gov with the Unique identifier: NCT03554941. Date of registration: (13/06/2018).

scholarly journals MEBO versus topical Diltiazem versus a combination of both ointments in the treatment of acute anal fissure: a randomized clinical trial protocol

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mohamad Hadi El Charif ◽  
Samer Doughan ◽  
Rawya Kredly ◽  
Sara Kassas ◽  
Rayan Azab ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Wound Healing ◽  
Anal Fissure ◽  
Topical Therapy ◽  
Trial Registration ◽  
Clinical Trial Registration ◽  
Anal Fissures ◽  
Link Type ◽  
Anorectal Region ◽  
Registration Date

Abstract Background Anal fissure is a common complication of the anorectal region and one of the most reported causes of anal pain. Acute anal fissure can be cured by surgery or medical treatment. There is an increase in the use of topical therapy for the treatment of anal fissures. A common topical drug used is Diltiazem (DTZ), a calcium-channel blocker, which relaxes the anal sphincter and thus promotes healing of the anal fissure. Moist exposed burn ointment (MEBO) is an ointment that is effective for the treatment of burns and wound healing and is becoming popular in the treatment of anal fissures. Methods This is a 1:1:1 randomized, controlled, parallel design, with endpoint measures of change in pain score, wound healing, defecation strain score and patient’s global impression of improvement. The study will be conducted at AUBMC over a 10-week period. Patients will be randomized to three treatment arms: MEBO, Diltiazem, and a combination of MEBO and Diltiazem ointments. Discussion The results of this study will allow physicians to assess the efficacy and safety of MEBO in the treatment of acute anal fissure, and also in comparison to Diltiazem. This trial will generate evidence-based conclusions regarding the use of a herbal/natural-based product (MEBO ointment) for the treatment of anal fissures. Trial registration ClinicalTrials.gov Identifier NCT04153032. Clinical Trial Registration Date: 06-NOVEMBER-2019.

scholarly journals Expression of inflammatory mediators in biofilm samples and clinical association in inflammatory bowel disease patients—a preliminary study

2021 ◽  
Author(s):  
Mayte Buchbender ◽  
Jakob Fehlhofer ◽  
Peter Proff ◽  
Tobias Möst ◽  
Jutta Ries ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Inflammatory Bowel Disease ◽  
Oral Cavity ◽  
Bowel Disease ◽  
Trial Registry ◽  
Clinical Trial Registry ◽  
Clinical Trial Registration ◽  
Expression Levels ◽  
Inflammatory Bowel ◽  
Group 2

Abstract Objectives Inflammatory bowel disease (IBD) has multiple impacts on soft and hard tissues in the oral cavity. The aim of this study was to analyze the expression of cytokines in biofilm samples from patients suffering from IBD and compare them to healthy patients. It was hypothesized that different cytokine expression levels and clinical associations might be drawn. Material and methods A total of 56 biofilm samples from three different patient cohorts (group 0 = healthy, HC n = 30; group 1 = Crohn’s disease, CD, n = 19; group 2 = ulcerative colitis, UC, n = 7) were examined for the expression levels of the cytokine interleukins IL-2, -6, and -10; matrix metalloproteinases 7 and 9; and surface antigens CD90/CD11a by quantitative real-time PCR and according to clinical parameters (plaque index, BOP, PD, DMFT, CAL). Relative gene expression was determined using the ∆∆CT method. Results The mean BOP values (p = 0.001) and PD (p = 0.000) were significantly higher in the CD group compared to controls. Expression of IL-10 was significantly higher in the CD (p = 0.004) and UC groups (p = 0.022). Expression of MMP-7 was significantly higher in the CD group (p = 0.032). IBD patients treated with TNF inhibitors (p = 0.007) or other immunosuppressants (p = 0.014) showed significant overexpression of IL-10 compared to controls. Conclusion Different expression levels of IL-10 and MMP-7 were detected in plaque samples from IBD patients. As only BOP was significantly increased, we conclude that no clinical impairment of periodontal tissue occurred in IBD patients. Clinical relevance With the worldwide increasing incidence of IBD, it is important to obtain insights into the effects of the disease on the oral cavity. The study was registered (01.09.2020) at the German clinical trial registry (DRKS00022956). Clinical trial registration The study is registered at the German clinical trial registry (DRKS00022956).

Clinical Trial Registration: The Time Has Come…

PM&R ◽  
2015 ◽  
Vol 7 (12) ◽  
pp. 1203-1204 ◽  
Author(s):  
Leighton Chan ◽  
Allen W. Heinemann
Keyword(s):  
Clinical Trial ◽  
Trial Registration ◽  
Clinical Trial Registration
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