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Project Title:  Test of Midodrine as a Countermeasure against Postflight Orthostatic Hypotension: SMO-006 Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 12/01/2009  
Task Last Updated: 01/18/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Platts, Steven H. Ph.D. / NASA Johnson Space Center 
Address:  Cardiovascular Laboratory 
Biomedical Research and Environmental Sciences Division 
Houston , TX 77058 
Email: steven.platts-1@nasa.gov 
Phone: 281-483-8177  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Key Personnel Changes / Previous PI: NOTE that Steven Platts took over as Principal Investigator from Janice Meck in FY2007. See Meck (Principal Investigator) for reports prior to FY2007.
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor: Goodwin, Thomas  
Center Contact:  
thomas.j.goodwin@nasa.gov 
Solicitation / Funding Source: Directed Research 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Flight Assignment/Project Notes: ISS 16, 17

Note deselected in October 2008, per JSC (4/2009)

NOTE: end date changed to 12/1/2009 per HRP Master Task List information dtd 1/12/2012 (Ed., 1/18/2012)

Task Description: After space flight the capability to remain upright (standing) may be compromised by an inability to maintain adequate cerebral perfusion. This condition, termed orthostatic hypotension, may result in presyncope (lightheadedness) or syncope (loss of consciousness) during reentry or egress from the space vehicle and for several days after landing. Approximately 20% of crewmembers on short-duration missions and 80% of those on long-duration missions experience presyncope during testing on landing day. To date, the potential countermeasures that have been tested (including lower-body negative pressure, fluid loading, Florinef, exercise) have not eliminated postflight orthostatic hypotension. Midodrine is a selective alpha-1 adrenergic agonist that is used clinically to treat orthostatic hypotension. It is almost completely absorbed after oral administration and is hydrolyzed enzymatically to its active metabolite, desglymidodrine, which has a bioavailability of 93%. Midodrine acts by increasing vaso- and venoconstriction, thereby decreasing peripheral venous capacity and blood pooling, but does not pass the blood-brain barrier and therefore has no central stimulant effects. The effect of midodrine as an alpha-adrenergic agonist may be particularly protective of orthostatic tolerance in astronauts who become presyncopal on landing day due to inadequate release of norepinephrine.

Midodrine was administered to crewmembers in the manner in which it might be used routinely after space flight. It was administered to five male astronauts 1 hour before landing, near the time of firing the Shuttle main engines to decelerate the Orbiter and begin its descent. The peak therapeutic effect of midodrine occurs approximately 1 hour after ingestion, making it particularly attractive as a landing-day countermeasure, such that its peak effect can be close to the time of the maximum gravitational forces during landing. The purpose of this report is to summarize the preliminary findings from this countermeasure evaluation. The strength of this study is that crewmembers participated in the postflight tilt test of orthostatic tolerance within 60 minutes after wheel stop, and therefore their physical status more closely represented their condition during reentry and immediately upon landing than when testing is conducted in the controlled environment of the baseline data collection facility. Testing in the baseline data collection facility typically occurs about two hours after wheels stop, following the astronauts’ walk-around of the vehicle and subsequent transport to the testing facility.

See also: http://www.nasa.gov/mission_pages/station/research/experiments/Midodrine-SDBI.html

Research Impact/Earth Benefits: In addition to benefits for astronauts, millions of people on Earth suffer from orthostatic hypotension and may benefit from information gained from this experiment.

Task Progress & Bibliography Information FY2010 
Task Progress: Eight male crewmembers volunteered to participate in this countermeasure evaluation. Three subjects withdrew from participation after the collection of preflight data. Two of these subjects were waived from participation: one had a prolonged QTc interval on an electrocardiogram during in-flight screening and one experienced significant neurovestibular disturbances on landing day. The third subject voluntarily withdrew from participation after the preflight midodrine tolerance test.

Approximately 90-days before flight, the participants will undergo a drug tolerance test for midodrine and will participate in a drug familiarization session. An operational tilt test will be conducted 10-days prior to launch, and the participants will complete a brief questionnaire before they leave the testing room.

In the course of this study, countermeasure subjects participated in a familiarization session and drug tolerance test, an 80 degree head-up tilt test without medications approximately 10 days before launch (L-10), and the tilt test protocol within 60 minutes of Shuttle landing (R+0). Subjects received verbal and written explanation of all procedures and signed statements of informed consent prior to participation. Preflight Activities

Approximately 10 days before launch (L-10), crewmembers participated in a tilt test in the JSC Cardiovascular Laboratory. Data were collected for 6 minutes while the subjects were supine, before they were tilted to 80 degrees head-up tilt using an automatic tilt table. The subjects remained in this position for 10 minutes, or until symptoms of orthostatic hypotension and/or presyncope occurred.

In-Flight Activities

Crewmembers participated in their scheduled in-flight activities without restriction for the duration of their Shuttle mission. After the decision for deorbit burn was confirmed on the scheduled landing day, crewmembers donned the Advanced Crew Escape Suit (ACES) and ingested 10 mg of midodrine approximately one 1 hour before the scheduled landing time. The midodrine pill and a cue card with medication instructions had been stowed in the subjects’ ACES for their convenience. All crewmembers participated in the standard oral fluid-loading protocol (equivalent to isotonic saline at a rate of 15 ml•kg-1 within 2 hours of landing) and inflated their antigravity suits during reentry and landing.

Postflight Activities

Postflight testing on landing day (R+0) was conducted on the Shuttle runway at either Kennedy Space Center, FL, or Dryden Flight Research Center, CA, in NASA’s Crew Transport Vehicle (CTV), a modified airport “people mover” used to transport the crewmembers from the Space Shuttle to the data collection facility. After Shuttle wheel stop, the CTV approached the Orbiter with the rest of the NASA convoy, and the Shuttle hatch was opened within ~20 min. After a brief medical check by the NASA flight surgeons, the crewmembers exited the Orbiter, with the midodrine test subjects exiting first. The subjects doffed their ACES within 5 min and participated in the same tilt test protocol as during the preflight assessment.

Summary

Midodrine appears to prevent orthostatic intolerance in test subjects after bed rest and in astronauts after space flight when testing is conducted in a controlled laboratory setting within 2 to 4 hours after landing. It is unclear at this time whether similar effects can be expected during reentry and immediately after landing, particularly in warmer environments and/or when the crewmembers are still wearing the ACES. Accurate interpretation of the current data requires that similar data be collected in control subjects (without midodrine) on the CTV. However, concerns about drug interactions with commonly used anti-emetics and prolonged QTc intervals observed in astronauts returning from long-duration missions make the routine use of midodrine unlikely and reliance on lower-body compression garments preferable.

Bibliography Type: Description: (Last Updated: 03/01/2018)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Shi S-J, Platts SH, Meck JV. "Promethazine counteracts the positive effects of midodrine on orthostatic intolerance." Presented at Experimental Biology 2006, San Francisco, California, April 1-5, 2006.

FASEB J. 2006 Mar;20 (Meeting Abstracts Supplement):A1252. http://www.fasebj.org/cgi/content/meeting_abstract/20/5/A1252?sid=c6503ac3-8082-4ad9-959c-cf84c69d88d6 , Mar-2006

Abstracts for Journals and Proceedings Platts SH, Shi S-J, Meck JV. "Midodrine exacerbates promethazine-induced akathisia." Presented at Presented at Experimental Biology 2006, San Francisco, California, April 1-5, 2006.

FASEB J. 2006 Mar;20 (Meeting Abstract Supplement):A1251-2. http://www.fasebj.org/cgi/content/meeting_abstract/20/5/A1251-d?sid=c6503ac3-8082-4ad9-959c-cf84c69d88d6 , Mar-2006

Abstracts for Journals and Proceedings Platts SH, Waters WW, Mitchell BM, Meck JV. "Midodrine prevents post-spaceflight orthostatic intolerance when administered 1 hour before tilt test." Presented at Experimental Biology 2004, Washington, DC, April 2004.

FASEB J. 2004;18(Meeting Abstract Supplement):A1207. , Apr-2004

Articles in Peer-reviewed Journals Platts SH, Ziegler MG, Waters WW, Meck JV. "Hemodynamic effects of midodrine after spaceflight in astronauts without orthostatic hypotension." Aviat Space Environ Med. 2006 Apr;77(4):429-33. PMID: 16676655 , Apr-2006
Articles in Peer-reviewed Journals Platts SH, Shi SJ, Meck JV. "Akathisia with combined use of midodrine and promethazine." JAMA. 2006 May 3;295(17):2000-1. PMID: 16670408 ; http://dx.doi.org/10.1001/jama.295.17.2000-b , May-2006
Project Title:  Test of Midodrine as a Countermeasure against Postflight Orthostatic Hypotension: SMO-006 Reduce
Fiscal Year: FY 2007 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2006  
End Date: 04/30/2009  
Task Last Updated: 04/15/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Platts, Steven H. Ph.D. / NASA Johnson Space Center 
Address:  Cardiovascular Laboratory 
Biomedical Research and Environmental Sciences Division 
Houston , TX 77058 
Email: steven.platts-1@nasa.gov 
Phone: 281-483-8177  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Key Personnel Changes / Previous PI: NOTE that Steven Platts took over as Principal Investigator from Janice Meck in FY2007. See Meck (Principal Investigator) for reports prior to FY2007.
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor: McCollum, Suzanne  
Center Contact: 281 483-7307 
suzanne.g.mccollum@nasa.gov 
Solicitation / Funding Source: Directed Research 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Flight Assignment/Project Notes: ISS 16, 17

Note deselected in October 2008, per JSC (4/2009)

Task Description: Many astronauts experience postflight orthostatic hypotension, a condition where the blood pressure drops when an individual stands up, resulting in presyncope (lightheadedness) or syncope (fainting). Approximately 20-30 percent of crews on short-duration (less than 20 days) missions and 83 percent of crews on long-duration missions experience some degree of orthostatic intolerance after return to Earth. To date, the countermeasures tested, such as fluid loading, the use of lower body negative pressure (LBNP), and Fluronef, have not successfully eliminated postflight orthostatic hypotension.

On Earth, the drug midodrine has been used extensively to treat low blood pressure. . Midodrine acts as a vasopressor (raise blood pressure) by causing constriction (tightening) of the blood vessels which leads to an increase in blood pressure. Test of Midodrine as a Countermeasure Against Post-flight Orthostatic Hypotension - Short Duration Biological Investigation (Midodrine-SDBI) studies the effectiveness of midodrine for the treatment of postflight orthostatic hypotension.

Operational Requirements

Crewmembers will ingest 10 milligrams of midodrine between Time of Ignition (TIG) and landing.

Operational Protocols

Approximately 90-days before flight, the participants will undergo a drug tolerance test for midodrine and will participate in a drug familiarization session. An operational tilt test will be conducted 10-days prior to launch, and the participants will complete a brief questionnaire before they leave the testing room.

See also: http://www.nasa.gov/mission_pages/station/research/experiments/Midodrine-SDBI.html

Research Impact/Earth Benefits: In addition to benefits for astronauts, millions of people on Earth suffer from orthostatic hypotension and may benefit from information gained from this experiment.

Task Progress & Bibliography Information FY2007 
Task Progress: No report received this reporting period. Task added to Task Book in April 2009, when received information from JSC that Principal Investigator changed to Steven Platts, from Janice Meck, in FY2007. See Meck (Principal Investigator) for reports prior to FY2007.

Bibliography Type: Description: (Last Updated: 03/01/2018)  Show Cumulative Bibliography Listing
 
 None in FY 2007