IU Indianapolis ScholarWorks :: Browsing by Subject "Clinical trials"

Browsing by Subject "Clinical trials"

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Biased ligand of the angiotensin II type 1 receptor in patients with acute heart failure: a randomized, double-blind, placebo-controlled, phase IIB, dose ranging trial (BLAST-AHF)
(Oxford University Press, 2017-08-07) Pang, Peter S.; Butler, Javed; Collins, Sean P.; Cotter, Gad; Davison, Beth A.; Ezekowitz, Justin A.; Filippatos, Gerasimos; Levy, Phillip D.; Metra, Marco; Ponikowski, Piotr; Teerlink, John R.; Voors, Adriaan A.; Bharucha, David; Goin, Kathleen; Soergel, David G.; Felker, G. Michael; Emergency Medicine, School of Medicine
Aims: Currently, no acute heart failure (AHF) therapy definitively improves outcomes. Reducing morbidity and mortality from acute heart failure (AHF) remains an unmet need. TRV027 is a novel 'biased' ligand of the angiotensin II type 1 receptor (AT1R), selectively antagonizing the negative effects of angiotensin II, while preserving the potential pro-contractility effects of AT1R stimulation. BLAST-AHF was designed to determine the safety, efficacy, and optimal dose of TRV027 to advance into future studies. Methods and results: BLAST-AHF was a multi-centre, international, randomized, double-blind, placebo-controlled, parallel group, phase IIb dose-ranging study, enrolling patients with AHF into 4 groups: placebo, 1, 5, or 25 mg/h of TRV027. Treatment was by IV infusion for 48-96 h. The primary composite endpoint was comprised of the following: (i) time from baseline to death through day 30, (ii) time from baseline to heart failure re-hospitalization through day 30, (iii) the first assessment time point following worsening heart failure through day 5, (iv) change in dyspnea visual analogue scale (VAS) score calculated as the area under the curve (AUC) representing the change from baseline over time from baseline through day 5, and (v) length of initial hospital stay (in days) from baseline. Analyses were by modified intention-to-treat. Overall, 621 patients were enrolled. After 254 patients, a pre-specified interim analysis resulted in several protocol changes, including a lower blood pressure inclusion criterion as well as a new allocation scheme of 2:1:2:1, overweighting both placebo, and the 5 mg/h dose. TRV027 did not confer any benefit over placebo at any dose with regards to the primary composite endpoint or any of the individual components. There were no significant safety issues with TRV027. Conclusion: In this phase IIb dose-ranging AHF study, TRV027 did not improve clinical status through 30-day follow-up compared with placebo.
Continuing Research During a Crisis
(Springer, 2021-04) Kroenke, Kurt; Bair, Matthew J.; Sachs, Greg A.; Medicine, School of Medicine
Development and evaluation of a web-based assent for adolescents considering an HIV vaccine trial
(Taylor & Francis, 2015-08) Blake, Diane R.; Lemay, Celeste A.; Maranda, Louise S.; Fortenberry, J. Dennis; Kearney, Margaret H.; Mazor, Kathleen M.; Department of Pediatrics, IU School of Medicine
HIV vaccine trials with minors will likely require parental permission and informed assent from adolescents. For this to be a valid process, the information needs to be presented in a manner that promotes adolescent comprehension. Previous studies suggest that adolescent comprehension of assent is often insufficient. We developed an interactive web-based assent that included interspersed quiz questions for a hypothetical HIV vaccine trial. Efficacy of the web-based assent was compared to a standard paper assent with and without interspersed questions. One hundred twenty teen participants, ages 15-17 years, from five community organizations were randomized to self-administered web-based assent (n=60) or investigator-administered paper assent with (n=29) or without (n=31) interspersed quiz questions. After reviewing the assent, participants completed a 27-item comprehension test. Comprehension scores were compared between groups. The mean number of correctly answered questions were 21.2 for the full paper group and 21.1 for the web-based group (t118=-0.08, p=0.94). Scores were 20.2 for the paper without interspersed questions sub-group and 22.1 for the paper with interspersed questions sub-group (t58=1.96, p=0.055). Participants in the web-based group performed as well on the comprehension test as those in the paper group, and those in the paper with questions sub-group performed better than those in the paper without questions sub-group, suggesting that interspersed quiz questions may improve understanding of a traditional paper assent. The minimal investigator time and standardized administration of the web-based assent as well as ability to tailor the assent discussion to topics identified by incorrect comprehension test responses are advantages worthy of further investigation.
Digital Cohorts Within the Social Mediome: An Approach to Circumvent Conventional Research Challenges?
(Elsevier, 2017-05) Kulanthaivel, Anand; Fogel, Rachel; Jones, Josette; Lammert, Craig; Biohealth Informatics, School of Informatics and Computing
Errors in self-reports of health services use: impact on alzheimer disease clinical trial designs
(Wolters Kluwer, 2015-03) Callahan, Christopher M.; Tu, Wanzhu; Stump, Timothy E.; Clark, Daniel O.; Unroe, Kathleen T.; Hendrie, Hugh C.; Department of Medicine, IU School of Medicine
BACKGROUND: Most Alzheimer disease clinical trials that compare the use of health services rely on reports of caregivers. The goal of this study was to assess the accuracy of self-reports among older adults with Alzheimer disease and their caregiver proxy respondents. This issue is particularly relevant to Alzheimer disease clinical trials because inaccuracy can lead both to loss of power and increased bias in study outcomes. METHODS: We compared respondent accuracy in reporting any use and in reporting the frequency of use with actual utilization data as documented in a comprehensive database. We next simulated the impact of underreporting and overreporting on sample size estimates and treatment effect bias for clinical trials comparing utilization between experimental groups. RESULTS: Respondents self-reports have a poor level of accuracy with κ-values often below 0.5. Respondents tend to underreport use even for rare events such as hospitalizations and nursing home stays. In analyses simulating underreporting and overreporting of varying magnitude, we found that errors in self-reports can increase the required sample size by 15% to 30%. In addition, bias in the reported treatment effect ranged from 3% to 18% due to both underreporting and overreporting errors. CONCLUSIONS: Use of self-report data in clinical trials of Alzheimer disease treatments may inflate sample size needs. Even when adequate power is achieved by increasing sample size, reporting errors can result in a biased estimate of the true effect size of the intervention.
Ethical Considerations for the Participation of Children of Minor Parents in Clinical Trials
(Springer, 2018-06) Ott, Mary A.; Crawley, Francis P.; Sáez-Llorens, Xavier; Owusu-Agyei, Seth; Neubauer, David; Dubin, Gary; Poplazarova, Tatjana; Begg, Norman; Rosenthal, Susan L.; Pediatrics, School of Medicine
Children of minor parents are under-represented in clinical trials. This is largely because of the ethical, legal, and regulatory complexities in the enrolment, consent, and appropriate access of children of minor parents to clinical research. Using a case-based approach, we examine appropriate access of children of minor parents in an international vaccine trial. We first consider the scientific justification for inclusion of children of minor parents in a vaccine trial. Laws and regulations governing consent generally do not address the issue of minor parents. In their absence, local community and cultural contexts may influence consent processes. Rights of the minor parent include dignity in their role as a parent and respect for their decision-making capacity in that role. Rights of the child include the right to have decisions made in their best interest and the right to the highest attainable standard of health. Children of minor parents may have vulnerabilities related to the age of their parent, such as increased rates of poverty, that have implications for consent. Neuroscience research suggests that, by age 12-14 years, minors have adult-level capacity to make research decisions in situations with low emotion and low distraction. We conclude with a set of recommendations based on these findings to facilitate appropriate access and equity related to the participation of children of minor parents in clinical research.
Evaluation of the burdens and benefits of participation in research by parents of children with life-limiting illnesses
(RCN Publishing, 2019-09-16) Hopper, Audrey; School of Nursing
BACKGROUND: Research is needed to improve care and diminish suffering for children with life-limiting illnesses and their parents. However, there are doubts about whether it is possible to conduct paediatric end of life research safely and ethically, as it may unduly burden or inadvertently harm participants. AIM: To compare and evaluate responses from participants to the assessments of burdens and benefits that were conducted at two timepoints during a phenomenological study that investigated parents' experiences of having a child with life-limiting cancer participate in a Phase I clinical trial. DISCUSSION: Parents reported that participating in the study was beneficial and resulted in minimal burden or distress. The assessment of benefits and burdens at the first timepoint appeared sufficient to understand participants' experiences. CONCLUSION: This study adds to the evidence that research may be safely and effectively conducted with parents of children who are deceased or have life-limiting illnesses. Further research is needed to evaluate the most effective timing of assessments of the burdens and benefits of their participation in research. IMPLICATIONS FOR PRACTICE: It is important when conducting research with people with life-limiting illnesses or their family members to assess the burdens and benefits of their participation, to understand their experiences and assist in its conduct.
The Hedgehog pathway: role in cell differentiation, polarity and proliferation.
(Springer, 2015-02) Jia, Yanfei; Wang, Yunshan; Xie, Jingwu; Department of Pediatrics, IU School of Medicine
Hedgehog (Hh) is first described as a genetic mutation that has "spiked" phenotype in the cuticles of Drosophila in later 1970s. Since then, Hh signaling has been implicated in regulation of differentiation, proliferation, tissue polarity, stem cell population and carcinogenesis. The first link of Hh signaling to cancer was established through discovery of genetic mutations of Hh receptor gene PTCH1 being responsible for Gorlin syndrome in 1996. It was later shown that Hh signaling is associated with many types of cancer, including skin, leukemia, lung, brain and gastrointestinal cancers. Another important milestone for the Hh research field is the FDA approval for the clinical use of Hh inhibitor Erivedge/Vismodegib for treatment of locally advanced and metastatic basal cell carcinomas. However, recent clinical trials of Hh signaling inhibitors in pancreatic, colon and ovarian cancer all failed, indicating a real need for further understanding of Hh signaling in cancer. In this review, we will summarize recent progress in the Hh signaling mechanism and its role in human cancer.
Inclusion of Adolescents in STI/HIV Biomedical Prevention Trials: Autonomy, Decision Making, and Parental Involvement
(American Psychological Association, 2018-09) Rosenthal, Susan L.; Morris, Marilyn C.; Hoffman, Lily F.; Zimet, Gregory D.; Pediatrics, School of Medicine
In order to develop new methods for prevention and treatment of sexually transmitted infection (STI) and human immunodeficiency virus (HIV), clinical trials must be conducted in relevant populations. In the U.S., half of all STI incident infections are among 15-24 year olds (Satterwhite et al., 2013), making healthy adolescents a highly relevant population. The inclusion of adolescents in STD/HIV prevention research is critical for developing appropriate strategies to promote adolescent sexual health. Results from adult studies may not generalize to adolescents, given their biological and psychosocial developmental status (Hwang et al., 2009). In order to understand the extent to which these differences are applicable to safety, efficacy, and acceptability, the products must be tested in minors. Enrolling adolescents who have not reached the legal age of majority in sexual health research, though, poses legal and ethical challenges. Investigators have been described as facing moral conflict between their responsibility to protect the scientific rigor of the study and the well-being of the participants (Merritt, 2005). Institutional Review Boards (IRBs) must balance the interests of minors, their parents, and the institution (Knopf et al., 2016). Data suggest that adolescents are under-represented in biomedical trials of HIV and STD prevention (Tolley et al., 2014; Hoffman et al., 2016). We propose that the inclusion of these adolescents in sexual health research is not only ethically permissible but is ethically required.
Introduction
(ScienceDirect, 2017-12) Miyamoto, Richard T.; Otolaryngology -- Head and Neck Surgery, School of Medicine

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