Gary Cutter
Institution:
Grant 5P50DE011147-030001 from National Institute Of Dental And Craniofacial Research
Abstract: Project 1 seeks to evaluate the effect of an antimicrobial agent applied to the mother s with the aim of reducing her levels of mutans streptococci M(MS) which, in turn, will decrease the likelihood of vertical transmission of MS to her infant. Our experience from a five year randomized trial (MITS) suggests the optimum time period for the applications of an agent so as to have an impact on the vertical transmission of MS. Previous studies provide sufficient information on the optimal concentration of chlorhexidine, an effective method of its delivery, and its efficacy in reducing oral MS levels. Total elimination or reduction of maternal oral MS over a time period should result in either; 1) a complete prevention of MS transmission or, 2) a lower degree of MS transmission or, 3) a delayed transmission of MS from mother to child. This in turn could result in a lower caries incidence in the child. In order to test the above hypotheses, a randomized active versus no treatment controlled clinical trial is proposed. Assuming the proportion of children with detectable levels of MS at 2 years of age is 16% in the treatment group, a total of 51 children are needed per group. To account for potential losses, a total of 64 infants will be included in each group. The trial will test the following two hypotheses 1) The application of the treatment agent to the mothers dentition at 3 months intervals from six months (generally prior to the time of the child s first tooth emergence) until the second birthday of the child will result in having a larger proportion of children with undetectable levels of oral MS in saliva samples in the treatment group compared to the untreated control group, and 2) The application of the treatment agent to the mothers dentition at 3 months intervals from the time of the child s first tooth emergence until the third birthday of the child will result in a decrease incidence of dental caries in children in the treatment group compared to the untreated control group. The treatment agent we will use is a combination of chlorhexidine and Sumatara benzoin. A layer of this varnish applied to all surfaces of teeth after a dental prophylaxis will be covered by another layer of polyurethane sealant in order to achieve sustained release and to prevent the bitter taste of chlorhexidine. Treatment mothers will be given new tooth brushes after each treatment to prevent a possible source of re- colonization, namely the old tooth brushes. Precautions will be taken to prevent lactating or pregnant mothers from being exposed to these agents. Basic demographic, oral bacteriological, medical, dental, and prenatal and post natal nutritional data will be collected and immunological profiles of mother-child pairs will be evaluated. These data would be analyzed to study the natural history of MS colonization as well as to evaluate the effectiveness of the therapeutic intervention. The proposed study is conducted among a group of subjects who belong to a population sub group who is at high risk for caries or who suffer the consequences of caries most. Despite one hundred years of research, dental caries still impact heavily on the nation and its economy, and if the proposed approach of preventing tooth decay succeeds, it would have major implications.
Keywords: Streptococcus mutans, antibacterial agent, chemoprevention, perinatal, preschool child (1-5), preventive dentistry, vertical transmission, chlorhexidine, dental caries inhibitor, human therapy evaluation, local antiinfective agent, mother child interaction, human subject
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Gary Cutter
University Of Alabama At Birmingham 1530 3rd Avenue South Birmingham, Al 35294
Grant 5P50DE011147-020001 from National Institute Of Dental And Craniofacial Research
Abstract: Project 1 seeks to evaluate the effect of an antimicrobial agent applied to the mother s with the aim of reducing her levels of mutans streptococci M(MS) which, in turn, will decrease the likelihood of vertical transmission of MS to her infant. Our experience from a five year randomized trial (MITS) suggests the optimum time period for the applications of an agent so as to have an impact on the vertical transmission of MS. Previous studies provide sufficient information on the optimal concentration of chlorhexidine, an effective method of its delivery, and its efficacy in reducing oral MS levels. Total elimination or reduction of maternal oral MS over a time period should result in either; 1) a complete prevention of MS transmission or, 2) a lower degree of MS transmission or, 3) a delayed transmission of MS from mother to child. This in turn could result in a lower caries incidence in the child. In order to test the above hypotheses, a randomized active versus no treatment controlled clinical trial is proposed. Assuming the proportion of children with detectable levels of MS at 2 years of age is 16% in the treatment group, a total of 51 children are needed per group. To account for potential losses, a total of 64 infants will be included in each group. The trial will test the following two hypotheses 1) The application of the treatment agent to the mothers dentition at 3 months intervals from six months (generally prior to the time of the child s first tooth emergence) until the second birthday of the child will result in having a larger proportion of children with undetectable levels of oral MS in saliva samples in the treatment group compared to the untreated control group, and 2) The application of the treatment agent to the mothers dentition at 3 months intervals from the time of the child s first tooth emergence until the third birthday of the child will result in a decrease incidence of dental caries in children in the treatment group compared to the untreated control group. The treatment agent we will use is a combination of chlorhexidine and Sumatara benzoin. A layer of this varnish applied to all surfaces of teeth after a dental prophylaxis will be covered by another layer of polyurethane sealant in order to achieve sustained release and to prevent the bitter taste of chlorhexidine. Treatment mothers will be given new tooth brushes after each treatment to prevent a possible source of re- colonization, namely the old tooth brushes. Precautions will be taken to prevent lactating or pregnant mothers from being exposed to these agents. Basic demographic, oral bacteriological, medical, dental, and prenatal and post natal nutritional data will be collected and immunological profiles of mother-child pairs will be evaluated. These data would be analyzed to study the natural history of MS colonization as well as to evaluate the effectiveness of the therapeutic intervention. The proposed study is conducted among a group of subjects who belong to a population sub group who is at high risk for caries or who suffer the consequences of caries most. Despite one hundred years of research, dental caries still impact heavily on the nation and its economy, and if the proposed approach of preventing tooth decay succeeds, it would have major implications.
Keywords: Streptococcus mutans, antibacterial agent, chemoprevention, perinatal, preschool child (1-5), preventive dentistry, vertical transmission, chlorhexidine, dental caries inhibitor, human therapy evaluation, local antiinfective agent, mother child interaction, human subject
Grants awarded to Gary Cutter
THYMECTOMY IN NON-THYMOMATOUS MG PATIENTS ON PREDNISONE
Gary Cutter
University Of Alabama At Birmingham, 1530 3rd Avenue South, Birmingham, Al 35294
Grant 2U01NS042685-06 from National Institute Of Neurological Disorders And Stroke
Abstract: The MGTX is a multi-center, single-blind, randomized study comparing thymectomy to no thymectomy in non-thymomatous myasthenia gravis (MG) patients receiving prednisone. This NINDS-sponsored project was initiated in September, 2005. The recruitment goal has been 200 subjects -100 to thymectomy plus prednisone and 100 to prednisone alone. This application is for renewal of this grant to extend the recruitment period for an additional two years and complete recruitment by November 2012 and follow patients for three years. The primary outcome and other outcome measures are unchanged from the original protocol. The plan is to continue recruitment and follow-up of all subjects, as randomized, with blinding being maintained until the last enrolled subject has completed all three years of the study. This plan is consistent from the original grant as approved by the study DSMB as well as the investigators, but will now have a longer follow-up for some patients (out to 6 years). For this renewal, we provide below the original specific aims, details of the study design, a study progress report including recruitment results and strategies to enhance recruitment to date, details of the study core components (Clinical Coordinating Center, Data Coordinating Center, and the associated Biomarker in MG study), details of all administrative activities, the baseline demographics of the study population, volume and quality of the data, a timeline for the completion of the study, and an overview of the current MG therapeutic arena and its impact on this study. The only changes we propose from the original study are to reduce the sample size from 200 to 150. The original sample size calculations were inflated to insure adequate sample sizes for anticipated drop-outs and subgroup hypotheses raised by the reviewers. This revision to 150 subjects is based on realistic estimates of our ability to recruit derived from a three-year experience of enrollment and the fact that the 150 total patients (70 additional in this request) remains adequate for our primary specific aim and can be completed within this budget request. The question being addressed by this study has challenged the MG community for over 50 years and this study is most likely the last time such a trial will be organized and/or completed
Keywords: 1, 2-Dehydrocortisone; Active Follow-up; Address; Budgets; Clinical; Communities; Data Coordinating Center; Data Coordination Center; Data Quality; Dehydrocortisone; Delta(1)-Cortisone; Deltacortisone; Deltadehydrocortisone; Drops; Enrollment; Goals; Grant; Investigators; Metacortandracin; Myasthenia Gravis; Out-patients; Outcome Measure; Outpatients; Patients; Population Study; Prednisone; Prednisonum; Pregna-1, 4-diene-3, 11, 20-trione, 17, 21-dihydroxy-; Progress Reports; Protocol; Protocols documentation; Randomized; Recruitment Activity; Research Design; Research Personnel; Researchers; SUBGP; Sample Size; Study Type; Subgroup; Therapeutic; Thymectomy; Time; TimeLine; base; biomarker; delta-Cortisone; demographics; enroll; experience; follow-up; primary outcome; public health relevance; randomisation; randomization; randomly assigned; recruit; study design
Project start date: 2002-01-01
Project end date: 2015-07-31
Budget start date: 30-SEP-2010
Budget end date: 31-JUL-2011
2U01NS042685-06 (2010): $995762
UAB PRE AND POST-DOCTORAL TRAINING PROGRAM IN BIOSTATISTICS
Gary Cutter
University Of Alabama At Birmingham, 1530 3rd Avenue South, Birmingham, Al 35294
Grant 5T32NS054584-04 from National Institute Of Neurological Disorders And Stroke
Abstract: The American College of Cardiology in testimony to US House of Representatives stated "In addition to expanding the number and scope of clinical trials, additional resources must be dedicated to train the next generation of clinical ´trialists´ in the areas of biostatistics, trial design, outcomes research, and bioethics". Another report stated "Fewer training programs...are available for statistics and biostatistics programs than ten years ago...In the mathematically based areas of bioinformatics, biostatistics... the shortage of qualified teachers and students going on to the life sciences is becoming acute... unless qualified faculty are replaced there will be increasingly fewer individuals with the necessary expertise to train the next generation of statisticians and computer scientists". Jim Ramsay, the President of the Statistical Society of Canada notes "Nick Fisher, the SSA President, struck a note of concern in his Presidential address. He cited declining memberships in the SSA, RSS, and ASA; [he also] noted the shrinking numbers of students entering statistics in Australia, and the disappearance of departments of statistics in universities in many countries. But at the same time there is an increasing demand for statisticians in academia, government and industry". The University of Alabama at Birmingham (UAB)´s Department of Biostatistics is well poised to help meet this need. Our department has undergone a renaissance in the past 5 years with significant strength in two areas Statistical Genetics and Clinical Trials. We have a large, well-funded, highly active department evenly split between methodological and applied research. Our focus on neurological diseases from Multiple Sclerosis, Myasthenia Gravis, Alzheimers, stroke, Parkinson´s, etc. provides a range of practical opportunities for advanced training. Our structured training program is designed to offer late pre- and post-doctoral fellowships to prepare scientists for careers in biostatistics specifically aimed at neurological research. The training program aims to develop independent investigative skills in the development, evaluation, and application of advanced statistical methods in neurological disorders and clinical trials. Applied experience is provided via co-mentorship by UAB´s well established NINDS-funded investigators. The importance of biostatistics in the public health of this nation cannot be overstated. Providing a well trained cadre to evaluate benefits and risks of treatment while dispelling the hype is a key public health endeavor
Keywords: Biometrics; Biometry; Biometry and Biostatistics; Biostatistics; Training Programs; post-doctoral training; postdoctoral training; statistics/biometry
Project start date: 2007-07-01
Project end date: 2012-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-02-109
5T32NS054584-04 (2010): $178525
5T32NS054584-03 (2009): $177151
THYMECTOMY IN NON-THYMOMATOUS MG PATIENTS ON PREDNISONE
Gary Cutter
University Of Alabama At Birmingham, 1530 3rd Avenue South, Birmingham, Al 35294
Grant 3U01NS042685-05S2 from National Institute Of Neurological Disorders And Stroke
Abstract: Myasthenia gravis (MG) is an autoimmune disease involving the thymus in which 85% of patients have antibodies to muscle acetylcholine receptors (AchR-Ab) that interfere with neuromuscular transmission and can cause severe, sometimes life-threatening, weakness. Thymectomy has been used world-wide to treat non-thymomatous MG, based on retrospective non-randomized studies. Prednisone (a corticosteroid) is also frequently used to treat MG. Both therapies are often employed together and both have adverse effects. Whether thymectomy benefits those who are also receiving prednisone is not known. To investigate the safety while comparing efficacy, we propose a multicenter, multiracial, international, single-blinded, 3-year duration clinical trial in which patients aged 18-60 years with generalized AchR-Ab positive non- thymomatous MG are randomized to receive extended transsternal thymectomy (ETTX) or no thymectomy. Both groups will receive prednisone administered by a ´blind´ evaluator according to the same set protocol aimed at establishing the minimum dose needed to achieve and maintain Minimal Manifestation (MM) status. The primary endpoint will comprise response and toxicity using a composite measuring clinical course, short and long term toxicities based on (a) clinical efficacy of therapy evaluated by the QMG weakness score (b) frequency of serious adverse events (c) the total dose of prednisone (Area under the Dose time Curve, AUDTC). A significant difference favoring ETTX would establish its clinical benefits in this patient population, and provide indirect evidence of the possible benefits of ETTX in patients not receiving prednisone medication. Conversely, failure to demonstrate a significant difference in the global or individual components of the primary endpoint would suggest that thymectomy is an unnecessary procedure in the population studied. Subgroup analysis may show whether benefits are confined to those who are prednisone naive at entry or in a particular age group. Thus the results will impact on current clinical practice
Keywords: 1, 2-Dehydrocortisone; 2-(Acetyloxy)-N, N, N-trimethylethanaminium; Acetylcholine; Address; Adjuvant; Adrenal Cortex Hormones; Adverse Experience; Adverse effects; Adverse event; Age Group Unspecified; Ancillary Study; Antibodies; Appointment; Area; Area Under Curve; Autoimmune Diseases; Cataract; Categories; Cholinergic Receptors; Cholinoceptive Sites; Cholinoceptors; Clinical; Clinical Trials; Clinical Trials, Unspecified; Corticoids; Corticosteroids; Cost Savings; Data; Dehydrocortisone; Delta(1)-Cortisone; Deltacortisone; Deltadehydrocortisone; Dose; Drugs; Ensure; Ethanaminium, 2-(acetyloxy)-N, N, N-trimethyl-; Evaluation; Experimental Designs; FLR; Failure (biologic function); Frequencies (time pattern); Frequency; Future; Gender; Health Care Providers; Health Personnel; Healthcare Providers; Healthcare worker; History; Human Resources; Immunotherapeutic agent; Individual; International; Investigators; Life; Literature; Manpower; Measurement; Measures; Medication; Metacortandracin; Monitor; Muscle; Muscle Tissue; Myasthenia Gravis; Operation; Operative Procedures; Operative Surgical Procedures; Osteoporosis; Outcome; Outcome Measure; Pain; Painful; Patient Monitoring; Patients; Pharmaceutic Preparations; Pharmaceutical Preparations; Plasma Exchange; Population Study; Prednisone; Prednisonum; Pregna-1, 4-diene-3, 11, 20-trione, 17, 21-dihydroxy-; Programs (PT); Programs [Publication Type]; Protocol; Protocols documentation; QOL; Quality of life; Questionnaires; Randomized; Receptor Protein; Receptors, ACh; Receptors, Acetylcholine; Recording of previous events; Research Design; Research Personnel; Researchers; Reticuloendothelial System, Thymus; Role; SAE; SUBGP; Safety; Sample Size; Saving, Cost; Serious Adverse Event; Study Type; Subgroup; Surgical; Surgical Interventions; Surgical Procedure; Symptoms; Therapeutic Corticosteroid; Thymectomy; Thymus; Thymus Gland; Thymus Proper; Time; Toxic effect; Toxicities; Treatment Side Effects; Unnecessary Procedures; age group; aged; autoimmune disorder; base; blind; cataractogenesis; cataractous lenses; clinical efficacy; clinical investigation; clinical practice; comparative efficacy; delta-Cortisone; design; designing; disability; dosage; drug/agent; evidence base; experience; failure; health care personnel; health care worker; health provider; healthcare personnel; human subject; immunologic preparation; immunotherapeutics; medical personnel; neuromuscular transmission; patient population; patient safety; personnel; primary outcome; programs; pyridostigmine; randomisation; randomization; randomized trial; randomly assigned; receptor; response; side effect; social role; study design; surgery; therapy adverse effect; treatment adverse effect; treatment provider
Project start date: 2005-09-23
Project end date: 2010-08-31
Budget start date: 1-SEP-2009
Budget end date: 31-AUG-2010
3U01NS042685-05S2 (2010): $71785
3U01NS042685-05S1 (2009): $75000
3U01NS042685-04S1 (2009): $1349862
Gary Cutter
University Of Alabama At Birmingham
Project start date: 2002-01-01
Project end date: 2015-07-31