{"project":{"acronym":"","projectId":23253,"title":"Monitoring of Bone Loss Biomarkers in Human Sweat: A Non-Invasive, Time Efficient Means of Monitoring Bone Resorption Markers under Micro and Partial Gravity Loading Conditions","primaryTaxonomyNodes":[{"taxonomyNodeId":10694,"taxonomyRootId":8816,"parentNodeId":10693,"level":3,"code":"TX06.3.1","title":"Medical Diagnosis and Prognosis","definition":"This functional area provides a suite of medical technologies, knowledge, and procedures that reduce the likelihood and/or consequence of both nominal and off-nominal medical events during exploration missions.","exampleTechnologies":"Emerging screening technologies, preventative countermeasures, low resource imaging modalities, laboratory analysis platforms and assays, sterile fluid generation, medication packaging options and long-term medication storage, medical equipment re-use and in-situ manufacturing, integrated medical equipment and software suite, autonomous clinical care and decision support","hasChildren":false,"hasInteriorContent":true}],"startTrl":4,"currentTrl":6,"endTrl":6,"benefits":"Loss of bone mass, density, and structural integrity is a significant health risk in a variety of populations such as the elderly, post-menopausal women, young female athletes, and astronauts. Such changes in overall bone quality lead to a greater risk of bone fracture and potentially a reduced rate of bone healing after injury. The ability to monitor biomarkers of bone remodeling (e.g., ionized calcium, collagen cross links) using sweat as an analytical sample provides an attractive alternative to the more invasive and costly measures presently employed such as a bone density scans by dual-energy X-ray absorptiometry (DXA), 24 hour urine collection protocols, or whole blood analyses. The development of a non-invasive, skin-mounted monitoring device which allows the quantitation of ionized calcium and/or collagen cross links in sweat will allow bone loss to be monitored in a wide variety of terrestrial populations that to date have not easily been monitored outside of a clinical setting. This particular project focuses on validating the concept that sweat analysis can be used as a non-invasive means of monitoring bone loss in crew members during periods of mechanical unloading under altered gravitational conditions. In addition, this project is also investigating the best technical approach to collecting a sweat sample which is specifically applicable to the space flight environment while utilizing well-accepted, clinically validated analytical methods. Development of a technology capable of real-time monitoring of biomarkers of bone loss that satisfies the criteria required for use in the space flight environment (i.e., non-invasive/non-intrusive, passive, small, light-weight, low power) has many direct applications in various populations here on Earth.
","description":"We propose to validate that the rate and extent of unloading-induced bone loss in humans can be assessed by monitoring the levels of two bone resorption markers in sweat, namely ionized calcium and collagen break-down products. Initial testing will be carried out in a young healthy population (at rest and during activity) and then in a clinical population undergoing active bone loss, namely spinal cord injury patients. All groups will include both male and female participants. Biomarker concentration will be determined in contemporaneous samples of sweat, blood, and urine collected during both short (24 hr) and long-term studies (multiple sessions over a period of months) to define the relationship between biomarker levels in the respective biological samples. Several different sweat collection techniques will be investigated to determine the most appropriate and efficient means of sample collection suitable for deployment during a space flight mission. These experiments will also include investigation of the most appropriate biomarker analysis techniques that allow for future deployment in micro- or partial gravity environments. This near-real-time monitoring approach may also provide the information required to justify modifying an ineffective bone loss countermeasure prescription during a mission. One of the approaches tested will be a novel, micro-fabricated fluid collection capillary array, known as the micro-fabricated sweat patch (MSP) device, specifically developed for use in microgravity. The MSP technology was initially developed because of its potential to become an autonomous, solid-state collection/analysis device worn on the skin of an astronaut requiring little or no crew interaction to perform its monitoring function. ","destinations":[{"lkuCodeId":1544,"code":"MOON_AND_CISLUNAR","description":"Moon and Cislunar","lkuCodeTypeId":526,"lkuCodeType":{"codeType":"DESTINATION_TYPE","description":"Destination Type"}},{"lkuCodeId":1518,"code":"MARS","description":"Mars","lkuCodeTypeId":526,"lkuCodeType":{"codeType":"DESTINATION_TYPE","description":"Destination Type"}}],"startYear":2008,"startMonth":5,"endYear":2012,"endMonth":5,"statusDescription":"Completed","principalInvestigators":[{"contactId":310965,"canUserEdit":false,"firstName":"Mark","lastName":"Clarke","fullName":"Mark Clarke","fullNameInverted":"Clarke, Mark","primaryEmail":"mclarke@mail.uh.edu","publicEmail":false,"nacontact":false}],"programDirectors":[{"contactId":103847,"canUserEdit":false,"firstName":"David","lastName":"Baumann","fullName":"David K Baumann","fullNameInverted":"Baumann, David K","middleInitial":"K","primaryEmail":"david.k.baumann@nasa.gov","publicEmail":true,"nacontact":false}],"programExecutives":[{"contactId":56,"canUserEdit":false,"firstName":"Stephen","lastName":"Davison","fullName":"Stephen C Davison","fullNameInverted":"Davison, Stephen C","middleInitial":"C","primaryEmail":"stephen.c.davison@nasa.gov","publicEmail":true,"nacontact":false}],"projectManagers":[{"contactId":187940,"canUserEdit":false,"firstName":"Jacilyn","lastName":"Maher","fullName":"Jacilyn S Maher","fullNameInverted":"Maher, Jacilyn S","middleInitial":"S","primaryEmail":"jacilyn.maher@nasa.gov","publicEmail":true,"nacontact":false}],"coInvestigators":[{"contactId":94424,"canUserEdit":false,"firstName":"Dan","lastName":"O'Connor","fullName":"Dan O'connor","fullNameInverted":"O'Connor, Dan","publicEmail":false,"nacontact":false}],"website":"https://taskbook.nasaprs.com","libraryItems":[{"files":[],"id":44627,"title":"Abstracts for Journals and Proceedings","description":"Clarke MS, Babcock LW, Diak D, O'Connor DP. \"Sweat Analysis for Assessment of Bone Loss Biomarkers.\" 2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012. 2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012., Feb-2012","libraryItemTypeId":1091,"projectId":23253,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":44628,"title":"Abstracts for Journals and Proceedings","description":"Clarke MS, Knoblauch MA, O'Connor DL. \"Monitoring of biomarkers of bone loss in human sweat - a non-invasive, time efficient means of monitoring bone resorption markers under micro- and partial gravity loading conditions.\" 2009 NASA Human Research Program Investigators’ Workshop, League City, TX, February 2-4, 2009. 2009 NASA Human Research Program Investigators’ Workshop, League City, TX, February 2-4, 2009. , Feb-2009","libraryItemTypeId":1091,"projectId":23253,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":44629,"title":"Abstracts for Journals and Proceedings","description":"Clarke MS, Knoblauch MA, O'Connor DL. \"Sweat and Biomarkers --can sweat be used to monitor biomarkers of bone loss?\" 2010 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 3-5, 2010. 2010 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 3-5, 2010., Feb-2010","libraryItemTypeId":1091,"projectId":23253,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":44630,"title":"Abstracts for Journals and Proceedings","description":"Clarke MS, Knoblauch MA, O'Connor DP. \"Monitoring Biomarkers of Bone Loss in Human Sweat.\" 18th IAA Humans in Space Symposium, Houston, TX, April 11-15, 2011. 18th IAA Humans in Space Symposium, Houston, TX, April 11-15, 2011., Apr-2011","libraryItemTypeId":1091,"projectId":23253,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}},{"files":[],"id":44631,"title":"NASA Technical Documents","description":"Clarke MS, Feeback DL. \"Microgravity-Compatible Sweat Collection and Analysis Device.\" MSC-23625-1 NASA Tech Briefs., Jul-2011","libraryItemTypeId":1091,"projectId":23253,"publishedDateString":"","contentType":{"lkuCodeId":1091,"code":"STORY","description":"Story","lkuCodeTypeId":341,"lkuCodeType":{"codeType":"LIBRARY_ITEM_TYPE","description":"Library Item Type"}}}],"transitions":[{"transitionId":7100,"projectId":23253,"partner":"Other","transitionDate":"2012-05-01","infusion":"Other","path":"Closed Out","details":"The overall goal of this project was to validate the concept that the rate and extent of unloading-induced bone loss in humans can be assessed by monitoring the levels of two bone resorption markers in sweat, namely ionized calcium (Ca2+) and total collagen cross-links (T-CCL) (i.e., the pyridinium cross-links PYD & DPD) The original funded project plan called for a phased approach consisting of three phases; the first phase focused on selection of the most appropriate and efficient means of collecting a sweat sample from an individual compatible with the microgravity environment of space flight coupled with biochemical validation that these sweat samples contained bone resorption markers at levels capable of being detected using standard laboratory analysis techniques; the second phase focused on validation of the concept that bone resorption marker levels detected in sweat samples accurately and consistently reflected circulating levels and/or urine levels of these biomarkers; and the third phase focused on longitudinal assessment of bone resorption marker level in sweat, blood, and urine in young and old populations undergoing active bone formation or bone loss, respectively. After successful completion of Phase I, preliminary data generated during Phase II indicated that the NASA criterion measure for bone loss during space flight (i.e., 24 hr urinary ionized calcium excretion), while related to calcium and T-CCL levels in sweat samples actively produced during defined exercise, were not predictive of 24 hr urine calcium excretion rates. After consultation and review of the preliminary Phase II results by representatives of the NASA-Johsnon Space Center-Human Research Program (JSC-HRP), the focus of Phase II was redirected to explore collection of a 24 hr sweat sample, rather than collection of a discrete, exercise-induced “active” sweat sample, to determine if a 24 hr integrated sweat sample was predictive of biomarker concentrations found in 24 hr urine samples. This redirection of effort required the identification and validation of additional commercially available absorbant materials which did not contain endogenous biomarker signal as well as a means of extracting the biomarkers from the absorbant material compatible with fluid handling limitations in the space flight environment. After identifying and developing such a collection method, this approach was then utilized to answer the question of whether or not biomarker levels in an integrated 24 hr sweat sample was predictive of those found in a concurrent 24 hr urine sample in a convenience of healthy individuals. After successful completion of Phase II, the NASA-JSC-HRP program indicated that they wished to deploy the sweat monitoring technology in a NASA bed-rest campaigns being performed at the GCRC at University of Texas Medical Branch (UTMB) instead of in young and old subject populations as originally planned. Unfortunately however, during the last 9 months of the project NASA had to postpone bed-rest operations resulting in a joint decision by NASA-HRP and the Principal Investigator to utilize spinal-injured patients recruited from the Texas Medical Center (rather than NASA bed rest subjects) in which to test the 24 hr sweat monitoring technology as means of assessing bone loss. The resulting time delay surrounding availability of bed rest subjects and the subsequent decision to utilize spinal chord injury (SCI) patients, coupled with the additional requirement to seek Committee for the Protection of Human Subjects (CPHS) approval for testing in a new subject population resulted in NASA granting a one year no-cost extension to the project. Limited data gathered in the final year of the project provides evidence that biomarker levels in a 24 hr integrated sweat sample are predictive of those levels found in 24 hr urine samples in SCI patients. These data indicate that 24 hr sweat sample collection (using a collection and analysis scheme compatible with space flight operations) in a terrestrial human population undergoing active bone loss in a similar fashion to crew members during space flight is a non-invasive, time-efficient alternative to on-orbit 24 hr urine void collection as means of assessing biomarkers of bone loss. In addition, the ability to perform this type of sample collection using a microgravity compatible approach to liquid sample handling and the use of simple colorimetric based analysis techniques is of notable operational relevancy. Our data and validated methodologies suggest that sweat biomarker analysis (as an operationally compatible means of assessing and/or monitoring bone loss in crew members during space flight) should be considered for further development as a “real-time” analytical method for assessment of space flight-induced bone loss and a valid means of monitoring the efficacy of “in-flight” bone loss countermeasures. [Editor's note 3/27/2013: No Task Book report received. Progress section and Bibliography compiled from PI's Final Technical Report submitted January 2013] ","rationale":"Other","infoText":"Closed out","infoTextExtra":"","dateText":"May 2012"}],"responsibleMd":{"acronym":"SOMD","canUserEdit":false,"city":"","external":false,"linkCount":0,"organizationId":9526,"organizationName":"Space Operations Mission Directorate","organizationType":"NASA_Mission_Directorate","naorganization":false,"organizationTypePretty":"NASA Mission Directorate"},"program":{"acronym":"HRP","active":true,"description":"Strategically, the HRP conducts research and technology development that: 1) enables the development or modification of Agency-level human health and performance standards by the Office of the Chief Health and Medical Officer (OCHMO) and 2) provides Human Exploration Operations Mission Directorate (HEOMD) with methods of meeting those standards in the design, development, and operation of mission systems.
HRP research focuses on reducing crew health and performance risks for exploration missions. In addition, HRP research gathers the data necessary to understand and mitigate the long-term health risks to the crew, to allow the update of specific crew health standards for each mission scenario, to support crew selection, and to address any rehabilitation requirements. The OCHMO owns and sets the standards upon which the HRP research efforts are based. The Transition to Medical Practice process defined by the OCHMO is used to review the HRP deliverable countermeasures and technologies prior to their operational use.
HRP technology development advances medical care and countermeasure systems for exploration and vehicle development programs’ missions. The HRP also develops and matures operational concepts to inform requirements for the design and operation of space vehicles and habitats needed for exploration. This includes requirements for displays and controls, internal environments, operations planning, habitability, and methodologies for maintaining crew physical and mental health as well as physical and cognitive capabilities.
The HRP is managed at the Johnson Space Center (JSC) and comprised of six research and technology development projects. These projects provide the program knowledge and capabilities to conduct research addressing the human health and performance risks as well as advancing the readiness levels of technology and countermeasures to the point of transfer to the customer programs and organizations. The six projects within the HRP are referred to as Program Elements throughout this document. Each Element is managed at the JSC with research and technology development expertise provided by JSC, Ames Research Center (ARC), Glenn Research Center (GRC), the Langley Research Center (LaRC), and the Kennedy Space Center (KSC), as well as other Agencies, institutions and organizations identified in the following Element descriptions. The six Elements are:
1) Space Radiation (SR) Element – The SR Element performs investigations to develop the scientific basis to accurately predict and mitigate health risks from the space radiation environment. This knowledge yields recommendations to permissible exposure limits, assessment/projection tools/models of crew risk from radiation exposure, and models/tools to assess vehicle design for radiation protection. The SR Element conducts research using accelerator-based simulation of space radiation. The SR Element explores and develops countermeasures to the deleterious effects of radiation on human health. The LaRC and ARC contribute to the SR Element.
2) Behavioral Health and Performance (BHP) Element – The BHP Element identifies and characterizes the behavioral and performance risks associated with training, living and working in space, and returning to Earth. The BHP Element develops strategies, tools, and technologies to mitigate these risks.
3) Exploration Medical Capability (ExMC) Element – The ExMC Element is responsible for defining requirements for crew health maintenance during exploration missions, developing treatment scenarios, extrapolating from the scenarios to health management modalities, and evaluating the feasibility of those modalities for use during exploration missions. The ExMC Element is also responsible for the technology and informatics development that will enable the availability of medical care and decision systems for exploration missions. GRC, LaRC and ARC contribute technology development and clinical care expertise to the ExMC Element.
4) Space Human Factors and Habitability (SHFH) Element – The SHFH Element is focused on the human system in space environments: how do humans interface with spacecraft systems, and what environmental and habitation factors are essential to maintain crew health and performance? The SHFH Element has three main focus areas: space human factors engineering, advanced environmental health, and advanced food technology. The ARC contributes to the SHFH Element.
5) Human Health Countermeasures (HHC) Element – The HHC Element is responsible for understanding the physiological effects of spaceflight and developing countermeasure strategies and procedures. The Element provides the biomedical expertise for the development and assessment of medical standards and vehicle and spacesuit requirements dictated by human physiological needs. In addition, the HHC Element develops a validated and integrated suite of countermeasures for exploration missions to ensure the maintenance of crew health during all mission phases. The ARC and GRC contribute to the HHC Element as well as international agencies cooperating on joint flight proposals, reduced gravity studies, and collaborative bed rest studies.
6) International Space Station Medical Projects (ISSMP) Element – The ISSMP Element is responsible for managing all ISS and ground analog human research activities, including those integrated with operational medical support of the crews, and to ensure research tasks are completed. The ISSMP is responsible for all planning, integration, and implementation services for HRP research tasks and evaluation activities requiring access to space or related flight resources on the ISS, Soyuz, Progress, Multi-Purpose Crew Vehicle (MPCV), commercial vehicles and ground-based spaceflight analogs. This includes support to related pre- and postflight activities. The ARC contributes to the ISSMP with technical support to experiment management, hardware development, and international partner integration. KSC provides support for baseline data collection requirements development for future crew vehicles.
The work performed within the six Elements is supported by numerous collaborative efforts with academia and international agencies. Relationships with the ISS Program, the National Space Biomedical Research Institute (NSBRI), the Brookhaven National Laboratory (BNL), and the University of Texas Medical Branch (UTMB) are critical to the HRP successfully meeting its objectives. The HRP also maintains collaborative relationships with the International Partners through various working groups. These relationships enhance the research capabilities and provide synergy between the research and technology efforts of different countries.
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