Phase II Study of Minocycline for Reducing Symptom Burden in Colorectal Patients
Ontology highlight
ABSTRACT: The goal of this clinical research study is to learn if minocycline can reduce numbness, pain, and/or loss of motor function in patients with colorectal cancer. In this study, minocycline will be compared to a placebo.
The study doctor can explain how the study drug is designed to work.
A placebo is not a drug. It looks like the study drug, but it is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.
Project description:These experiments are designed to discover genes that are expressed selectively by synaptic nuclei in skeletal muscle with the particular goal of identifying genes that regulate motor axon growth and differentiation. We plan to isolate RNA from the dissected synaptic region of skeletal muscle and from the non-synaptic region of skeletal muscle and to identify the genes that are expressed at higher levels in the synaptic than non-synaptic region. Previously, we showed that motor axons fail to stop and differentiate in mice lacking MuSK, a receptor tyrosine kinase that is activated by motor neuron-derived Agrin. We hypothesize that MuSK activation normally leads to the production of a retrograde stop/differentiation signal that is encoded by a gene that is expressed preferentially in synaptic nuclei. In the absence of MuSK signaling, the retrograde signaling is not produced by synaptic nuclei, and consequently motor axons wander aimlessly over the muscle. We obtain 6 to 8 micrograms of total RNA from the dissected synaptic or non-synaptic region from a single P21 mouse diaphragm muscle. This is a standard procedure in the lab, and we have used these methods to analzye gene expression and to generate high-quality cDNA libraries. Because the synaptic zone is narrower in the left hemi-diaphragm, we will isolate RNA from this half of the diaphragm. In order to isolate sufficient RNA (5 micrograms from each sample), we will pool the synaptic and non-synaptic regions from two hemi-diaphragms. In order to reduce experimental variability, we wish to analzye expression in six samples: three samples of synaptic RNA and three samples of non-synaptic RNA. We will ship the isolated RNA samples to the Consortium in order to generate labeled cDNA, to screen Affymetrix mouse oligo arrays and to assist in the analysis. Several genes, including the subunits of the acetylcholine receptor, MuSK, acetylcholinesterase, and utrophin are known to be expressed preferentially in synaptic nuclei; thus, these genes serve as internal controls for the reliability and effectiveness of the screen. Most other genes, several of which we have analyzed in previous studies, including actin, GAPDH, runx1, nogoC, creatine kinase, etc. are expressed uniformly in skeletal muscle; thus, expression of these genes should be equally represented in synaptic and non-synaptic regions. Keywords: other
Project description:Genetic variations in drug metabolising enzymes play a role in how individuals respond to drugs. Pharmacogene variation data in the Ghanaian population is limited and this study looks at exploring common variations that exist in our population for commonly used drugs. In addition, the study also looks at the how variations in cytokines and HLA play a role in HBV pathogenesis. Samples were validated with PCR-RFLP for accuracy
Project description:Genetic variations in drug metabolising enzymes play a role in how individuals respond to drugs. Pharmacogene variation data in the Ghanaian population is limited and this study looks at exploring common variations that exist in our population for commonly used drugs. Samples were validated with PCR-RFLP for accuracy
Project description:Breast cancer (BC) is the most common malignancy and the leading cause of cancer mortality in women. It is possible that signals arising from the gut microbiome are protective in BC. We used common drugs designed to turn on pathways to mimic one major signal coming from gut microbes, namely bile acids. Taking advantage of a drug called Ocaliva, which is commercially available for another disease, we repurposed this drug to test its anti-cancer potential. Ocaliva worked on a specific protein target called FXR to reduce tumor growth and kill cancer cells. In contrast, a similar drug that targets a different protein called TGR5 was not effective in killing cancer cells. Taken together, these findings suggest that using Ocaliva or other bile acid signals derived from the gut microbiome to target the protein FXR could be an important new therapeutic strategy for individuals with aggressive BC.
Project description:This dataset looks at the transcriptome of in vitro-differentiated primary lung cells infected with SARS-CoV2. Some cells have been treated with the drug Enzalutamide.
Project description:REMICADE (infliximab) is a drug used to treat active Crohn’s disease and is being tested in an experiment to see if it may be useful in preventing relapse of Crohn’s disease after surgical resection. This study will compare the effects (both good and bad) of REMICADE (infliximab) to those of placebo. Placebo looks like the drug being studied but has no active ingredients.
Project description:Lockwood2006 - AlzheimersDisease PBPK
model
A mathematical model to predict the
effectiveness of CI-1017 (muscarinic agonist) for Alzheimer's
disease by evaluating changes in ADAS-cog score.
This model is described in the article:
Application of clinical
trial simulation to compare proof-of-concept study designs for
drugs with a slow onset of effect; an example in Alzheimer's
disease.
Lockwood P, Ewy W, Hermann D,
Holford N.
Pharm. Res. 2006 Sep; 23(9):
2050-2059
Abstract:
OBJECTIVE: Clinical trial simulation (CTS) was used to
select a robust design to test the hypothesis that a new
treatment was effective for Alzheimer's disease (AD).
Typically, a parallel group, placebo controlled, 12-week trial
in 200-400 AD patients would be used to establish drug effect
relative to placebo (i.e., Ho: Drug Effect = 0). We evaluated
if a crossover design would allow smaller and shorter duration
trials. MATERIALS AND METHODS: A family of plausible drug and
disease models describing the time course of the AD assessment
scale (ADAS-Cog) was developed based on Phase I data and
literature reports of other treatments for AD. The models
included pharmacokinetic, pharmacodynamic, disease progression,
and placebo components. Eight alternative trial designs were
explored via simulation. One hundred replicates of each
combination of drug and disease model and trial design were
simulated. A 'positive trial' reflecting drug activity was
declared considering both a dose trend test (p < 0.05) and
pair-wise comparisons to placebo (p < 0.025). RESULTS: A 4 x
4 Latin Square design was predicted to have at least 80% power
to detect activity across a range of drug and disease models.
The trial design was subsequently implemented and the trial was
completed. Based on the results of the actual trial, a
conclusive decision about further development was taken. The
crossover design provided enhanced power over a parallel group
design due to the lower residual variability. CONCLUSION: CTS
aided the decision to use a more efficient proof of concept
trial design, leading to savings of up to US 4 M dollars in
direct costs and a firm decision 8-12 months earlier than a
12-week parallel group trial.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000673.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
Project description:The CLARITY trial (NCT00213135) was designed as a double-blind, placebo-controlled study to allow the best comparison of absolute efficacy and safety of oral cladribine in RRMS subjects. 1326 patients with relapsing MS were randomized (1:1:1) to receive cladribine tablets 3.5 mg/kg or 5.25 mg/kg bodyweight or placebo. Gene expression data in whole blood samples at 96 weeks were prepared according to standard Affymetrix protocols Gene expression data in whole blood samples at 96 weeks were available from patients randomized to placebo (n=57), cladribine tablets 3.5 mg/kg (n=62), and cladribine tablets 5.25 mg/kg (n=70).