CBR Research Grants
Project Summaries—2007
2011—2010—2009—2008—2007—2006—2005—2004—2003—2002—2001—2000—1999—1998—1997—1996—1995
Lipid Metabolism in Gestational Diabetics Pregnancy results in a transient hyperlipidemic state. To date there have been limited prospective longitudinal investigations to determine whether subgroups of women have different lipid alterations during pregnancy. Another physiologic metabolic disturbance noted during pregnancy is insulin resistance. Increased production of placental factors such as human placental lactogen and placental growth hormone cause a blunting of insulin function. In a small group of women, the pancreatic reserve is limited and insulin production is unable to maintain a euglycemic environment. This condition, known as gestational diabetes mellitus (GDM), can result in maternal and fetal hyperglycemia. It is unknown at this time if women with GDM have an increased lipid response during pregnancy. But if this is the case, it could identify a subset of women who are at increased risk for metabolic syndrome. The metabolic syndrome is a collection of metabolic disorders including obesity, hypertension, hyperlipidemia, insulin resistance, and elevated glucose concentrations. The purpose of this pilot study is to determine if, during pregnancy, women with GDM have an exaggerated lipid response compared to non-gestational diabetics. If a difference is noted, further studies will explore the possibility of screening gestational diabetics during their pregnancy for hyperlipidemia to determine if prenatal screening can predict postpartum risk for hyperlipidemia. In addition the relationship, if any between maternal lipid dysfunction and placental disease will be explored. This will be a prospective cohort study. As part of routine prenatal care, women receive a one hour glucose challenge test to screen for gestational diabetes. Those women with elevated values then require a three hour glucose tolerance test, which is a diagnostic test for gestational diabetes. All women that are scheduled to receive a three hour GTT at a Baystate Reference Laboratory phlebotomy office will be identified and ask to enroll in this study. 46 women whose three hour GTT is normal and thus do not have GDM, will be compare to 46 women with an abnormal three hour GTT and thus would have the diagnosis of GDM. Enrolled women will have a lipid panel consisting of; total cholesterol, triglyerides, HDL and LDL cholesterol at the time of their fasting glucose blood sample. In addition, a repeat lipid panel will be sent at the time of the third hour sample, to assess changes, if any due to the glucose challenge. Women in both the GDM and normal groups will be asked to return 6-8 weeks postpartum to obtain a fasting lipid profile. The primary outcome variables will be lipid levels in normal and GDM women. These values will be measured at baseline (time of the GTT test) and at 6-8 weeks postpartum. Secondary outcome variables will include changes in lipid levels after a glucose challenge along with perinatal complications and placental pathologic findings between the two groups. Effective date: July 2007 Placebo vs. Extended Release Stimulant Crossover Trial in Preschoolers with ADHD This investigator hopes to have a career examining psychopharmacologic and behavioral interventions for preschool aged youth with disruptive behavioral disorders. This award would allow the investigator to pursue necessary additional training to gain research skills and experience in preparation for a K award application, which will be instrumental to this applicant's eventual goals of becoming an independent, successful, clinical child psychiatry researcher. In a pilot study under a training grant to this investigator, preschool three-to-five year olds rigourously diagnosed with Attention Deficit/Hyperactivity Disorder (ADHD) will be recruited from a general child psychiatry clinic to enroll into a small (approximately 30 children), 6 week double-blind, crossover comparison trial of extended release mixed amphetamine salts (XR-MAS) versus placebo to study efficacy and safety tolerance. The specific aim is to evaluate safety and efficacy data of XR-MAS versus placebo in children who will experience both medications in a brief study period. The recently completed NIMH-funded multisite Preschool ADHD Treatment Study (PATS) demonstrates that short-acting MPH can be safe and effective in reducing core symptoms of ADHD, but there is no data for providers to consider intiating MAS versus MPH. Recent pharmacoepidiemiological data indicates prescribers are increasingly using both types of stimulants in this population, though there is a dearth of controlled studies evaluating these medications in preschool children. It is proposed that XR-MAS will have a favorable safety and efficacy profile, and that this pilot study, followed by a larger K award study, could demonstrate that under short term study conditions, XR-MAS are reasonably well tolerated and effective in particularly young and developmentally vulnerable children at risk for poor educational, social and physical outcomes. The importance of demonstrating and comparing XR-MAS versus placebo in this population is due to ADHD being a public health burden amongst preschool children as indicated in recent reports this population is 3 to 5 times more likely to be expelled from daycare settings as adolescents are from high school. Additionally, this study and the training proposal will help this investigator become an early career scientist who can investigate the short and long term risks and benefits regarding the use of psychotropic medication in developmentally vulnerable children. The data from this small study will be used in a K award application to further investigate strategies to minimize symptom burden and functional impairment in this vulnerable population. Two years of this research fellowship will provide me with the additional training and skills necessary to pursue a career in child psychiatry intervention research. My career goal is to make significant contributions to a specific understudied population in pediatric psychiatry (preschool youth with disruptive behavior disorders) by investigating the safety and efficacy of different psychosocial and pharamacologic interventions, either alone or in combination, in these children. This fellowship will allow me to conduct necessary clinical research projects that will help generate pilot data for future projects, including ultimately a K award application. I need additional training and experience in clinical interventional research. Specifically I need dedicated time to learn more about research design and methodology, data collection and analysis, and publication and dissemination of results to further my ulitmate goal of developing an independent research career. In addition to my specific research study, I will be engaged in focused course work in bio-statistics at a nationally recognized university, as well as collaborating on a NIMH funded longitudinal study of preschool youth with disruptive behavioral disorders awarded to one of my consultants. These activities, in addition to meetings and reviews with my consultants, will prepare me to meet the expectations of becoming an independent investigator as well as establish me and my clinic for future collaborative projects of public health importance with other leaders in the field. Effective date: July 2007 DMBT-1 Expression, Atypical Hyperplasia and Gail Model Risk This is a cross-sectional study of approximately 280 women at the Breast Center and the Pioneer Valley Surgery Center who underwent breast biopsy with a finding of atypia or reduction mammoplasty with a finding of benign. Analyses are of variations in the expression of two hypothesized biomarkers of breast cancer risk, DMBT-1 and COX-2 among the two groups, “reduction mammoplasty controls” and “atypia only cases”. Additional analyses explore the covariation of DMBT-1 and COX-2 expression with Gail Model risk scores, the latter being the standard of risk assessment in breast cancer prevention. Rationale for this project is our overall objective of identifying biomarkers that predict progression of pre-malignant breast lesions. Effective date: July 2007 Testosterone and Cognition: A nonhuman primate model An increasing number of men use testosterone without sufficient knowledge of its effect on the brain and cognition. The relationship between testosterone and cognition is difficult to address in humans because of confounding factors inherent to human studies, as well as health concerns related to the use of sex steroids in eugonadal people. Nonhuman primates, such as rhesus monkeys (Macaca mulatta) have proven to be excellent models in which to study the effects of estrogens on female cognition, but similar studies in males are critically lacking. The present study will investigate the activational effects of testosterone on cognitive function for the first time in adult male nonhuman primates. The aims of the study are to (1) evaluate the relationships between endogenous testosterone levels and cognitive function (2) examine the effects of chemical castration and add-back of testosterone on cognition (3) determine whether the cognitive effects of testosterone are mediated by changes in motor function and/or emotional reactivity. Young adult male rhesus monkeys will be repeatedly tested on a battery of cognitive, motor and emotional tasks at different time points throughout the one year study: 1) at baseline, during the breeding season (relatively high testosterone levels) 2) when treated with a gonadotropin releasing hormone agonist which completely suppresses gonadal activity 3) with add-back of testosterone or placebo 4) when intact during the non-breeding season (relatively low testosterone levels). The data should provide new insights into the actions of androgens on cognition and lay the foundation for long-term studies of the effects of sex hormones on age-related cognitive decline. The use of nonhuman primates in this endeavor should be particularly useful to foster the development of sex-specific approaches to treatment and prevention of age-related cognitive decline. Effective date: September 2007 |
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