
Azacitidine Plus Deferasirox (ICL670) in Higher Risk Myelodysplastic Syndromes (MDS)
Myelodysplastic SyndromesMyelodysplastic syndromes are common blood disorders that can affect as many as one in 1000 Canadians over the age of 65. They are characterized by low blood counts that require frequent blood transfusions. The development of iron overload in these patients is inevitable. The iron deposits in vital organs such as the heart and the liver and can lead to organ dysfunction. Deferasirox is a well-studied drug that helps remove iron from the body. Most people with this disorder die due to progression of their disease to acute leukemia through multiple mechanisms. Iron overload in patients with myelodysplastic syndromes has been shown to be associated with shorter survival, and potentially a higher chance of leukemia. In a certain sub-group of higher risk patients, the drug azacitidine has been shown to decrease the chance of progression to leukemia and death from it. Thus, it is presently the standard of care for these patients. However, 50% of higher risk patients are still unresponsive to this medication, leaving a large group of patients for which other treatment options are emergently needed. Given that a large proportion of higher risk MDS patients fail to respond to azacitidine, and the evidence that iron deposition may lead to increased leukemic transformation, we would like to study whether iron removal from the body with deferasirox potentiates azacitidine in its effects on overall survival, as well as the chance of leukemia transformation. This question needs to be addressed in a randomized controlled trial, and the first step is a preliminary study to determine if the combination of azacitidine and deferasirox has any biologic effect. This study will determine whether this combination leads to blood count improvement over azacitidine alone. If this drug combination ultimately proves more useful than azacitidine alone with respect to survival, this has the potential to impact the care of a large proportion of patients with myelodysplastic syndromes.

Preventing Alcohol Withdrawal Syndrome With Oral Baclofen
Alcohol Withdrawal SyndromeAdult medical/surgical inpatient hospital care is more difficult and more expensive when complicated by alcohol dependency (AD), especially for patients who develop alcohol withdrawal syndrome (AWS). AWS can be mild, moderate or severe. The Severity of Ethanol Withdrawal Scale (SEWS) is tool used to assess severity and is the current standard of care for both monitoring and treating AWS at Denver Health. Moderate/severe AWS (i.e., SEWS ≥ 7) has important clinical implications and requires pharmacological treatment. At present, there are no safe and effective options for preventing AWS in at-risk inpatients. Baclofen is a GABA-B receptor agonist that has been used in the alleviation of spasticity in patients with multiple sclerosis since the 1970s. Baclofen has shown promise in the management of alcohol dependency in preclinical and clinical studies. We propose to examine baclofen in the prevention/amelioration of AWS in adult medical inpatients. The investigators hypothesize that Baclofen, as compared to placebo, will significantly reduce the number of adult inpatients with AD who will develop moderate/severe AWS (SEWS ≥ 7) when assessed at 72 hours after enrollment. Further the investigators hypothesize that Baclofen, as compared to placebo, will significantly reduce the need for symptom-triggered benzodiazepine administration during the 72 hours of hospitalization. These hypotheses will be tested in adult inpatients who are determined to be at risk for alcohol withdrawal and are subsequently placed on the SEWS monitoring and treatment protocol. These patients will be randomized to baclofen 10mg three times daily vs placebo.

Ticagrelor vs Clopidogrel in Non-ST Elevation Acute Coronary Syndrome Patients Undergoing PCI With...
Non-ST Elevation Acute Coronary SyndromeThe purpose of this study is to determine if ticagrelor is as effective as clopidogrel in rate of onset and degree of platelet inhibition for patients with non-ST elevation of acute coronary syndrome (NSTE-ACS) undergoing ad hoc percutaneous coronary intervention (PCI) with bivalirudin.

Randomized Controlled Trial of Ketamine Infusion With Continuous Epidural Infusion for Treatment...
Complex Regional Pain SyndromeThe purpose of this study is to determine whether epidural and ketamine infusions are effective in the treatment of Complex Regional Pain Syndrome (CRPS).

Manual Therapy to Treat Gluteus Medius Trigger Points
Anterior Knee Pain SyndromePatellofemoral Pain SyndromeThis is a blinded randomized controlled trial to assess the effectiveness of manual therapy to improve hip abduction strength in patients with acute anterior knee pain. The primary objective of this study is to see if manual therapy to the gluteus medius can significantly alter within-session measurements of hip abductor strength in patients with anterior knee pain. The secondary objective of this study is to see if manual therapy to the gluteus medius can significantly alter within session pain in patients with anterior knee pain.

Treatment of Complex Regional Pain Syndrome With Once Daily Gastric-Retentive Gabapentin (Gralise)...
Complex Regional Pain Syndrome I (CRPS I)The purpose of this study is to see if an FDA-approved drug (Gralise) can help people with certain types of neuropathic pain without causing too many side effects.

An Open Label Extension Study in Subjects With Fragile X Syndrome
Fragile X SyndromeThis study will enroll subjects who have completed Protocols 209FX301, 209FX302, or are currently participating in Protocol 2202 into a long-term study in which all subjects will receive active drug (arbaclofen).

A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed...
Myelodysplastic SyndromesMyelogenous Leukemia1 moreThis study will assess the safety and efficacy of vismodegib in patients with relapsed/refractory acute myelogenous leukemia (AML) and relapsed/refractory high-risk myelodysplastic syndrome (MDS). Patients in Cohort 1 will receive single-agent vismodegib 150 mg orally daily. In Cohort 2, patients will receive vismodegib 150 mg orally daily in combination with cytarabine 20 mg subcutaneously for 10 days. Anticipated time on study treatment is until disease progression, intolerable toxicity, or patient withdrawal of consent.

Pharmacogenetics of Clopidogrel in Acute Coronary Syndromes
Acute Coronary SyndromesThe antiplatelet agent clopidogrel is an effective drug for the prevention of thrombotic events in patients with acute coronary syndromes, and is therefore one of the most frequently prescribed drugs worldwide. Accumulating data suggest that the response to clopidogrel is characterised by significant inter-patient variability in the degree of platelet inhibition and the risk of cardiovascular events. Recent research findings have highlighted the role of genetic variations in determining antiplatelet response variability, and this has aroused interest in genotyping all thienopyridine-eligible patients in order to identify those who would be at increased risk of harm if treated with clopidogrel. This is a prospective, multicentre, randomised study enrolling consecutive patients hospitalised because of an ACS with or without ST-segment elevation. The patients are randomised to undergo or not tests for CYP2C19*2, CYP2C19*17 and ABCB1 3435 genetic variants immediately after diagnosis. The genotyping is done using a Q3 System (a compact platform that enables the classic laboratory analysis of DNA by means of real-time PCR). The Q3 has been designed as a low entry-cost, portable, point-of-care instrument for foolproof use by unskilled personnel. The patients randomised to the pharmacogenomic arm receive one of the ADP receptor antagonists (clopidogrel/prasugrel/ticagrelor) on the basis of an algorithm that consider genetic and clinical variables. The patients randomised to the standard treatment arm receive clopidogrel or prasugrel or ticagrelor on the basis of the standard of care (clinical algorithm alone). For each patient, a record is made of the occurrence of cardiovascular death, non-fatal MI, stroke, BARC-defined bleeding, and definite or probable stent thrombosis. The primary endpoint is the composite of death due to cardiovascular causes, non-fatal MI and stroke. The secondary endpoints is the occurrence of definite or probable stent thrombosis, and BARC-defined major bleeding events (types 3-5).

Clinical Trial Assessing the Efficacy and Safety of BP1.4979 in Restless Legs Syndrome
Restless Legs SyndromeThis is a Group Sequential Test multicenter, randomized, double blind, placebo controlled phase II proof of concept trial with parallel groups to evaluate the efficacy and the safety of BP1.4979 15mg BID compared to placebo in RLS patients during 2 weeks double blind treatment.