NASA 80JSC024R0002 Questions and Answers.pdf

Questions and Answers

General statement regarding the specific tests and protocols for the study:

This RFQ is only for the platform portion of the Flywheel Exercise study, meaning that it requires availability of certain facilities, capabilities and equipment as well as the processes and expertise to utilize the capabilities to support general bedrest study requirements per the SOW. The specific science requirements for the study will be defined in a follow-on contract. For this RFQ, we expect offerors to describe the capabilities and equipment available through their facility, including details that could impact availability and use for the study. Additionally, the offerors will describe the implementation of a trial run to demonstrate the required capabilities and processes to support bedrest, including the development of timelines that satisfy requirements within stated constraints while resolving potential negative interactions between test/measures. The specific science tests/measures to be implemented during the study bedrest periods, the number of tests, the protocols for the tests, etc. will be detailed in the science contract and the selected platform vendor will have the opportunity to provide a cost proposal for the additional services to meet the science requirements. This platform RFQ is intended to provide the basic bedrest capabilities including conducting a trial run of the facility, general subject care for the bedrest study periods, and integration of requirements into an overall bedrest study implementation. The science contract will cover the implementation of the specific study requirements.

Recruitment:

Question: What is the inclusion/exclusion criteria for Age, Sex, BMI, Race, Medication exclusions and Stratums?

Answer: Attachment 1 section A1 of the RFP includes the general inclusion/exclusion criteria for HRP bedrest studies and serves as the initial criteria for subject screening. The follow-on Science contract will include the study specific inclusion/exclusion criteria (if different) that will be used for the final subject screening and determination of acceptability for the study. It is expected that recruiting (with appropriate IRB approval) will be conducted to assemble a pool of candidates that meet the general I/E criteria before the study specific

I/E criteria is provided (and study IRB approvals) for informed consent for screening and subject selection.

Question: What qualifies as a demonstrable dentist certificate?

Answer: A statement from the subject’s dentist that there are no known dental issues requiring treatment before the conclusion of the study or that should impact the subject’s participation in the bedrest study.

- Question: What qualifies as demonstrable medical insurance?

- Answer: Proof of existing medical insurance coverage that expires after the participant’s completion of the study.

- Question: What is acceptable for an official certificate of absence of criminal background?

- Answer: A standard commercial criminal background check is sufficient. Financial background is generally not checked.

- Question: How is the assessment of ocular exclusion criteria performed?

- Answer: Visual acuity (normal range) with and without corrective lenses (if worn) should be tested, as well as testing of color vision as inability to differentiate between colors may be exclusionary for some studies that require it. Depth perception, refraction, phoria/tropia measurements have not been required in recruitment for previous studies.

Imaging- MRI

- Question: Is there an acquisition protocol ?

- Answer: This will be defined in the science protocol.

- Question: At what timeID(s) will the participant complete ultrasound?

- Answer: For this RFQ, please describe the MRI capabilities available for use in this study, with any restrictions or considerations such as limited hours of operation. It is expected that MRI scans will be included in the trial run to demonstrate operations in HDT as well as to ensure the quality of the scans meet HRP expectations for the study.

- Question: Will there be a window for day of acquisition or will weekend scans be a potential requirement?

- Answer: For the trial run, it is expected that MRIs will be scheduled within an agreed timeframe (e.g., trial day 2 at 10:00am +/- 6 hours). The science protocol will include requirements for the bedrest periods, which could necessitate imaging during weekends depending upon the subject enrollment process utilized (rolling enrollment for instance) and other study parameters. Study requirements include implementation windows (+/-days) where appropriate to facilitate flexibility and implementation.

- Question: Will we need to do any post processing/ analysis? If so, is there a protocol?

- Answer: The science protocol will define requirements for specific measures, including post processing and analysis. For the purposes of this platform RFQ, assume there is no requirement for MRI post-processing or analysis for the MRIs performed during the trial run.

Imaging- Ultrasound

- Question: Acquisition protocol – The documents state “muscle ultrasound”, but what muscle(s)? And what measurements are required?

- Answer: The science protocol will define requirements for specific measures. If the facility capability does not support ultrasound of certain muscle groups or under certain conditions, please include that information in the response.

- Question: Is the time of day for ultrasound acquisition critical? Is there a window for day of acquisition?

- Answer: The science protocol will include requirements for the bedrest periods, which could necessitate imaging at various times of day and during weekends depending upon the subject enrollment process utilized (rolling enrollment for instance) and other study parameters. Study requirements include implementation windows (+/- days) where appropriate to facilitate flexibility and implementation. In general, tests/measures are expected to be performed for all subjects on the same day of bedrest, which may not be the same calendar day due to the enrollment process and other factors. The timing of measures on a given day is planned to avoid confounds with other activities and work within study constraints.

Intervention

- Question: Will the equipment for exercise (fly wheel) be provided or does the site need to purchase?

- Answer: The flywheel exercise device will be provided by HRP as it is the actual device that will be used for astronaut training for the Artemis program. HRP will work with the selected vendor to optimize the installation and implementation of the flywheel exercise device for

HDT operations.

Exercise

- Question: How many VO2max tests will be performed through the dura�on of the study?

- Answer: For this RFQ, VO2max tes�ng is expected to be performed on each subject during the trial run while in HDT posi�on. VO2max tes�ng is also performed as part of Bedrest Standard

Measures performed during pre- and post-HDT, although implementa�on of standard measures is covered by the science contract, not the pla�orm contract. The science protocol will define requirements for specific study measures.

- Question: What mode of exercise that will be u�lized for VO2 max tes�ng. Assuming it will be cycle ergometry.

- Answer: For Bedrest Standard Measures, maximum aerobic capacity is assessed using a graded exercise protocol on a cycle ergometer. The graded exercise protocol provides an individualized approach to achieve subjects’ maximum aerobic capacity using small increments in workload.

During tes�ng, subjects maintain a pedaling cadence of 70 to 75 revolu�ons per minute (rpm).

Workload begins at 50 Wats for three (3) minutes and is then increased by 25W every minute.

Increasing workload in small increments with each minute of exercise allows for evalua�on of ven�latory threshold and VO2max. Using this protocol, maximal exercise is achieved in approximately eight (8) to 15 minutes.

- Question: Will the exercise equipment be provided to run the VO2max tes�ng?

- Answer: The selected vendor is expected to provide all the equipment needed for VO2max tes�ng.

- Question: We have metabolic carts , but what addi�onal equipment needs to be u�lized for the

HDT VO2max tes�ng.

- Answer:

o LODE electronic cycle ergometer and controller is preferred o Parvomedics True One 2400 metabolic gas analyzer (contractor can subs�tute similar hardware) o Quinton Q-Stress 12-Lead ECG heart rate monitor (contractor can subs�tute similar hardware) o Crash cart in the immediate vicinity

- Question: Will any special monitoring during the VO2max need to take place such as ECG monitoring, pulse oximetry, blood pressures, etc ?

- Answer: Heart rate is monitored con�nuously during res�ng (ECG monitor). Blood pressure is measured during exercise, using a sphygmomanometer and stethoscope. Measures collected

(or derived) through gas exchange data include VO2, carbon dioxide elimina�on (VCO2), respiratory exchange rate (RER), minute ven�la�on (Ve), anaerobic threshold and ven�latory threshold. Workload is also recorded. An addi�onal measure collected may include con�nuous finger arterial blood pressure (photoplethysmography device). Surface EMG of seven leg muscles is also measured during the test.

Clinical Chemistry

- Question: What biospecimens (blood, urine, stool, saliva, hair, nail, nasal) will be collected and what is the frequency?

- Answer: For the trial run, only the sample collec�on process is assessed without specimens being evaluated. The science protocol will define requirements for specific study measures.

- Question: Will samples be stored, sent to a biorepository, or sent to a Central reference lab?

Answer: The science protocol will define requirements for specific study measures. Since we are not collecting data from the Trial Run there is no requirement for sample storage.

- Question: What biospecimen tes�ng will be conducted onsite?

- Answer: The science protocol will define requirements for specific study measures.

- Question: What tests will be performed for inclusion/exclusion and will tes�ng be performed onsite?

- Answer: See the list of screening tests added at the end of this document.

- Question: What safety labs will be collected throughout the trial and where will tes�ng be performed?

- Answer: Medical monitoring requirements are specified by the IRB and should be arranged by the Head Medical Doctor for the study. Safety Monitoring should include:

o Daily ward rounds by medical staff, supported by nutri�onists and study nurse, will be recorded o Body temperature (oral body temperature measurement using a commercially available digital thermometer) will be recorded o Heart rate, respira�on rate and oscillometric arterial blood pressure (systolic, diastolic and mean arterial pressure) are measured immediately following the scheduled wake-up and recorded o Body weight (BW) is assessed daily following the first urine void of the day and will be recorded o Urine volume as 24h pools will be recorded o Throughout the study, selected 24h urine pools and venous blood samples will be analyzed once during the adapta�ons phase (e.g., BDC-14), once during the HDT phase

(e.g., HDT10) and twice during the in-house sta�onary recovery phase (e.g., R+1, R+10).

Tes�ng should be performed by the Facility.

Inpatient/ Outpatient

- Question: At what time IDs will participants complete OCT procedure?

- Answer: For the trial run, it is expected that an OCT will be conducted on each subject in the HDT position. The selected vendor is expected to develop the timeline for the trial run within the agreed constraints, for the purpose of demonstrating the vendor’s capability to integrate multiple constraints and resolve negative interactions between study measures.

The science protocol will define requirements for specific study measures.

- Question: Is there a protocol for frequency of physical therapy during the reconditioning phase?

- Answer: Currently we recommend the following as part of our Bedrest Standard Measures:

Facility designated personnel will evaluate subjects at the beginning of the pre-bed rest phase and upon re-ambulation. Using this evaluation, a unique protocol for reconditioning is developed. Standard reconditioning exercises include aerobic conditioning, plyometrics, balance, cone walks, strength, abdominals, and stretching. Seven days of reconditioning is a minimum; facility designated personnel will modify the length and exact schedule of the protocol as needed for the progression of each subject. Reconditioning exercises are introduced in a baseline familiarization session and then occur daily R+4 through R+11.

Screening Test Requirements Tables 4 through 6 identify the screening tests that subjects will be required to pass before they can be admitted to the study.

Table 1 Screening Tests: Blood

Red cell Distribution Width (RBW) AT III

White Blood cells S-Akt

Eosinophils Protrombinmut Lupus-PTT

Neutrophils Ferritin

Lymphocytes F-V-Leiden

Monocytes Factor II

Basophils TSH

Red Blood cells T3

Hemoglobin T4

Hematocrit Retinol

Mean Corpuscular Volume (MCV) Beta-carotene

Platelet Count Serum phylloquinone (Vit. K)

Fasting Glucose Alpha-Tocopherol/Gamma Toco (Vit. E)

Creatinine Glutathione reductase erythrocyic (Vit. B1)

Uric acid Vitamin B6

Urea Folate

Total Bilirubin Vit. C

Aspartat Aminotransferase (AST = GOT) Vit. B12

Alanin Aminotransferase (ALT = GPT) 25-OHD (Vit D)

Glutamyl transferase (GGT) Serum iron

Alkaline Phosphatase (AP) Transferrin

Total Protein Saturated transferrin (calculated)

Albumin Transferrin receptor

Cholesterol Selenium

High density Lipoprotein Copper

Low Density Lipoprotein Zinc

Triglyzeride pH

Chloride pO2, pC02

Sodium HCO3 -, Base Excess (BE) (calculated)

Potassium HIV

Calcium Hepatitic B and C

C reactive protein (CRP) Tuberculosis Quantiferon Gold

Factor I Protein C and S Activities

Prothrombin mutants Factor VIII-activity

Only on spec:

Free Testosterone (men)

FSH (women)

LH (women)

Estradiol (women)

Passing value: Normal range and/or physicians’ assessment

In case low ferritin or vitamin levels are the only criterion in the clinical-chemical screening, which would lead to exclusion from the study, the volunteer should take an individual supplementation recommended by the Head Medical doctor and the Nutritional Lead for the two months prior to the start of the study.

In case of a Vitamin D deficiency, the following scheme will be applied:

Total loading dose depends on the basal D3 levels and body weight (Aloia et al., Am J Clin Nut 2008) and is calculated according to the formula:

(IU) = 40 x (75-25-OH-D3 (nmol/L) x body mass (kg))

Ferritin and Vitamin D levels will be retested immediately before the start of the study. Should the lowest permissible levels still not be attained, the affected volunteer is excluded from the study.

Table 2 Screening Tests: Urine pH Bilirubin

Specific Gravity Urobilinogen

Appearance Nitrite

Ketones Leukocyte

Protein Illegal drugs

Glucose Nicotine

Blood Pregnancy test

Passing value: Normal range and/or physicians’ assessment or negative result (drug and nicotine, pregnancy)

Table 3 Screening Tests: Others

Screening Test Performed By

Value Assessed for

Inclusion Passing Value

Bone densitometry – single scan of hip and lumbar spine

:envihab

T-score No less than 1.5 SD below based on T-score

Resting electrocardiogram

(ECG)

Laboratory normal values per ASCP

Physician’s assessment

Cycle ergometer stress test

:envihab Laboratory normal values per ASCP

Physician’s assessment

Stand test :envihab Normal Values Physician’s assessment

Screening Test Performed By

Value Assessed for

Inclusion Passing Value

Visual acuity obtained with and without corrective lenses (if worn). Testing of color vision using visuals from Cognition test protocols as inability to differentiate between the colors will be exclusionary. Depth perception, refraction, phoria/tropia measurements are not required (protocol-specific).

Normal Values Normal range

MRI Screening Questionnaire

:envihab

OCT (Block scan retina and circle scan around the optic nerve head)

:envihab Physician’s assessment

Within normal range

Visual acuity obtained with and without corrective lenses

:envihab Physician’s assessment

Within normal range

Tonometry/Intraocular pressure (IOP)

:envihab Physician’s assessment

Within normal range

Fundus examination, including Papilla examination

:envihab Physician’s assessment

Within normal range

Objective refraction :envihab Physician’s assessment

Within normal range

Acoustic Reflex Threshold test

:envihab PI requirement </=95

Psychological Screening:

In general, test subjects will be tested and interviewed by an experienced psychologist to ensure that they have the mental fitness necessary to complete all aspects of the respective bed rest study.

As an example, this is the current psychological screening plan for bedrest subjects at :envihab:

The psychological screening comprises an initial paper pencil test on biography and personal history of the subjects (Biomed questionnaire) and a personality test specifically developed for bed rest screening by the Institute of Aerospace Medicine’s Aviation and Space Psychology Division, based on the previously used FPI-R (Freiburger Persönlichkeitsinventar) questionnaire and Big Five personality factors. As part of further psychologic evaluation, following medical screening, subjects also fill out a standardized test on personality (TSS – Temperament Structure Scales (Maschke, 1986), and a DLR questionnaire on compliance. The final selection of the tests that will be used in the screening process shall be done by the psychologist who will perform the psychological screening. These tests will be followed by a face-to-face interview. The final selection of the subjects will be a joint decision of the psychologist or psychiatrist and the project lead.

Screening Test Requirements