Dataset Information

Evaluation of Efficacy and Safety Using Low Dose Radiation Therapy with Alzheimer's Disease: A Protocol for Multicenter Phase II Clinical Trial.

ABSTRACT:

Background

Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disease resulting from extracellular and intracellular deposits of amyloid-β (Aβ) and neurofibrillary tangles in the brain. Although many clinical studies evaluating pharmacological approaches have been conducted, most have shown disappointing results; thus, innovative strategies other than drugs have been actively attempted.

Objective

This study aims to explore low-dose radiation therapy (LDRT) for the treatment of patients with AD based on preclinical evidence, case reports, and a small pilot trial in humans.

Methods

This study is a phase II, multicenter, prospective, single-blinded, randomized controlled trial that will evaluate the efficacy and safety of LDRT to the whole brain using a linear accelerator in patients with mild AD. Sixty participants will be randomly assigned to three groups: experimental I (24 cGy/6 fractions), experimental II (300 cGy/6 fractions), or sham RT group (0 cGy/6 fractions). During LDRT and follow-up visits after LDRT, possible adverse events will be assessed by the physician's interview and neurological examinations. Furthermore, the effectiveness of LDRT will be measured using neurocognitive function tests and imaging tools at 6 and 12 months after LDRT. We will also monitor the alterations in cytokines, Aβ42/Aβ40 ratio, and tau levels in plasma. Our primary endpoint is the change in cognitive function test scores estimated by the Alzheimer's Disease Assessment Scale-Korea compared to baseline after 6 months of LDRT.

Conclusions

This study is registered at ClinicalTrials.gov [NCT05635968] and is currently recruiting patients. This study will provide evidence that LDRT is a new treatment strategy for AD.

SUBMITTER: Kim DY

PROVIDER: S-EPMC10578208 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluation of Efficacy and Safety Using Low Dose Radiation Therapy with Alzheimer's Disease: A Protocol for Multicenter Phase II Clinical Trial.

Kim Dong-Yun DY Kim Jae Sik JS Seo Young-Seok YS Park Woo-Yoon WY Kim Byoung Hyuck BH Hong Eun-Hee EH Kim Ji Young JY Cho Seong-Jun SJ Rhee Hak Young HY Kim Aryun A Kim Keun You KY Oh Dae Jong DJ Chung Weon Kuu WK

Journal of Alzheimer's disease : JAD 20230101 3

<h4>Background</h4>Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disease resulting from extracellular and intracellular deposits of amyloid-β (Aβ) and neurofibrillary tangles in the brain. Although many clinical studies evaluating pharmacological approaches have been conducted, most have shown disappointing results; thus, innovative strategies other than drugs have been actively attempted.<h4>Objective</h4>This study aims to explore low-dose radiation therap ...[more]

PMID: 37638435

Similar Datasets

Project description:BackgroundThe objective of focal brachytherapy (BT) is to provide effective prostate cancer control for low-risk disease but with reduced genitourinary, gastrointestinal and sexual side effects in a cost-effective way.ObjectiveThe aim of this study is to describe a phase II study examining technical and dosimetric feasibility and toxicity, quality of life changes, and local control with post-treatment biopsy outcomes in men with early stage low volume prostate cancer treated with focal iodine-125 seed BT.MethodsThe study design is a prospective, multicenter trial with a planned sample size of 20 patients including men with a minimum age of 60 years, a life expectancy estimated to be greater than 10 years, with low or low-tier intermediate risk prostate cancer, unilateral disease on the biopsy, and a Gleason score of ≤3+4 and <25% cores involved. The investigations specific for the study are multi-parametric magnetic resonance imaging (Mp-MRI) baseline, at 20 and 36 months to rule out high grade disease and a transperineal mapping biopsy (baseline and at 36 months) for more accurate patient selection. The hemigland region will receive 144 Gy. Standard normal tissue constraints will be considered as for a whole gland (WG) implant. Dosimetric parameters will be evaluated at day 30 after the implant. Toxicity and quality of life will be evaluated with international validated questionnaires focusing on urinary, rectal, sexual domain, and general health-related quality of life. The patients will complete this assessment at baseline and then approximately every 6 months after the implant up to 10 years.ResultsTo date, one patient is involved in the trial. He underwent the pre-implant investigations which found bilateral disease. Therefore, a standard seed implant was performed. If the results from this trial provide evidence that the treatment is safe, feasible, and improves toxicity, funding will be sought to conduct a large, multicenter, randomized controlled trial (RCT).ConclusionsThis protocol is designed to show feasibility in delivering hemigland focal therapy with seed BT. It may answer crucial questions and obtain data which will enable downstream decisions on focal low dose rate (LDR) prostate BT.ClinicaltrialClinicaltrial.gov NCT02643511; https://www.clinicaltrials.gov/ct2/show/NCT02643511 (Archived by Webcite at http://www.webcitation.org/6ghLCzIhY).

Project description:BackgroundThe COVID-19 pandemic is expected to cause significant morbidity and mortality. The development of an effective vaccine will take several months to become available, and its affordability is unpredictable. Transfusion of convalescent plasma (CP) may provide passive immunity. Based on initial data from China, a group of hematologists, infectious disease specialists, and intensivists drafted this protocol in March 2020.ObjectiveThe aim of this study is to test the feasibility, safety, and efficacy of CP in treating patients with COVID-19 across Saudi Arabia.MethodsEligible patients with COVID-19 will be recruited for CP infusion according to the inclusion criteria. As COVID-19 has proven to be a moving target as far as its management is concerned, we will use current definitions according to the Ministry of Health (MOH) guidelines for diagnosis, treatment, and recovery. All CP recipients will receive supportive management including all available recommended therapies according to the available MOH guidelines. Eligible CP donors will be patients with COVID-19 who have fully recovered from their disease according to MOH recovery criteria as detailed in the inclusion criteria. CP donors have to qualify as blood donors according to MOH regulations except for the history of COVID-19 in the recent past. We will also test the CP donors for the presence of SARS-CoV-2 antibodies by a rapid test, and aliquots will be archived for future antibody titration. Due to the perceived benefit of CP, randomization was not considered. However, we will compare the outcome of the cohort treated with CP with those who did not receive CP due to a lack of consent or lack of availability. In this national collaborative study, there is a likelihood of not finding exactly matched control group patients. Hence, we plan to perform a propensity score matching of the CP recipients with the comparator group patients for the major characteristics. We plan to collect demographic, clinical, and laboratory characteristics of both groups and compare the outcomes. A total sample size of 575 patients, 115 CP recipients and 460 matched controls (1:4 ratio), will be sufficient to detect a clinically important hospital stay and 30-day mortality difference between the two groups with 80% power and a 5% level of significance.ResultsAt present, patient recruitment is still ongoing, and the interim analysis of the first 40 patients will be shared soon.ConclusionsIn this paper, we present a protocol for a national collaborative multicenter phase II study in Saudi Arabia for assessing the feasibility, safety, and potential efficacy of CP in treating patients with severe COVID-19. We plan to publish an interim report of the first 40 CP recipients and their matched comparators soon.Trial registrationClinicalTrials.gov NCT04347681; https://clinicaltrials.gov/ct2/show/NCT04347681.International registered report identifier (irrid)PRR1-10.2196/23543.

Project description:BackgroundFruquintinib has demonstrated significant improvement in overall survival (OS) among previously treated metastatic colorectal cancer (mCRC) patients. However, the utilization of fruquintinib has been constrained by various toxicities, such as hand-foot skin reaction (HFSR) and hypertension, particularly in elderly patients with reduced tolerance to the standard dosage. This study aims to investigate the efficacy and safety of fruquintinib dose-escalation strategy for elderly refractory mCRC patients.Patients and methodsThis open-label, single-arm, phase II trial included patients aged 65 years or over with mCRC who had progressed after two or more lines of chemotherapy. Fruquintinib was administered for 21 consecutive days of a 28-day treatment cycle. The starting dose of fruquintinib was 3 mg/day and escalated to 4 mg/day in Week 2 and 5 mg/day in Week 3 if no significant drug-related toxicity was observed. The highest tolerated dose from Cycle 1 would be administered in Cycle 2 and all subsequent cycles. Before commencing treatment, all enrolled patients underwent a G8 questionnaire and comprehensive geriatric assessments. The primary endpoint of the study was progression-free survival (PFS).ResultsA total of 29 patients were enrolled and all started fruquintinib at 3 mg/day. Fifteen patients (51.7%) were subsequently escalated to 4 mg/day and 4 (13.8%) to 5 mg/day. Only four (13.8%) patients discontinued treatment due to adverse events (AEs). The median PFS was 3.8 months (95% CI, 2.7-4.9), and the median OS was 7.6 months (95% CI, 6.5-8.7). Treatment-related adverse events (TRAEs) were observed in all 29 patients (100%). The most frequently occurring (>10%) TRAEs greater than Grade 3 were HFSR (20.7%), hypertension (20.7%), and diarrhea (10.3%).ConclusionOur study indicated that a dose of 4 mg/day was well tolerated by most elderly patients, suggesting that fruquintinib dose-escalation strategy during the first cycle could serve as a viable alternative to the standard 5 mg/day dosing.

Dataset Information

Evaluation of Efficacy and Safety Using Low Dose Radiation Therapy with Alzheimer's Disease: A Protocol for Multicenter Phase II Clinical Trial.

Background

Objective

Methods

Conclusions

Publications

Evaluation of Efficacy and Safety Using Low Dose Radiation Therapy with Alzheimer's Disease: A Protocol for Multicenter Phase II Clinical Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets