DTIC ADA420330: The Efficacy of Modafinil for Sustaining Alertness and Simulator Flight Performance in F-117 Pilots During 37 Hours of Continuous Wakefulness

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by  Defense Technical Information Center

—_—_———e United States Air Force
Research Laboratory
aE Ra ee ee

THE EFFICACY OF MODAFINIL FOR
SUSTAINING ALERTNESS AND
SIMULATOR FLIGHT PERFORMANCE IN
F-117 PILOTS DURING 37 HOURS OF
CONTINUOUS WAKEFULNESS

John Caldwell
Lynn Caldwell
Jennifer Smith
Linda Alvarado:
Tara Helntz
Jeffery Mytar
David Brown

HUMAN EFFECTIVENESS DIRECTORATE
BIOSCIENCES AND PROTECTION DIVISION
FATIGUE COUNTERMEASURES BRANCH

2485 GILLINGHAM DRIVE
BROOKS GITY-BASE TX 78235-5105

Aanuary 2004

—_____——___
[Aupreved fr public release, distribution unlimited
| Avproved fr blierelewse, disuibulion uulimites |

20040226 104.
Novices
‘This report is published in the inberast of sclentific and technica! Information
‘exchange and does not constitute approval ar disapproval of Its Ideas or findings.

‘Thi report is published as racaived and has not been edited by the publication
staff of the air Farce Research Laboratory,

Using Government drawings, specifications, or other data included in this
doaiment for any purpose other than Government related procurement does not in
‘any way obligate the US Government. The fact that the Government formulated ar
supplied the drawings, specificatians, ar other data, does nat license the holder or
Any other person or corporation, or convey any rights oF permission to manufacture,
se, or stl any patented invention that may relate to them.

‘The Office of Public affairs has reviewed this paper, and it releasable to the

National Technical infonnation Service, where it will be available to te general
‘ublis, nduding foreign nationals.

‘This raport has been reviewed and is approved for publication,

ASIGNEDI

{JOHN A, CALDWELL, Ph.D.
Project Selentiet

SIGNED}!

THOMAS L, CROPPER Col USAF, BSC
chief, Biosciences and Protection Division
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‘TABLE OF CONTENTS,

BACKGROUND
‘The Casses of Farigne ip Operational Contexts
‘The Ieppact of Fatigue on Military Performance .
Fatigue Remedies for Operational Setings
‘Nonpharmavological Strategies
‘Pharmacofogical Strategies
‘Amiphetariines

OBLECTIVES.
METHODS...
Subjects
Apparat
‘Compound robe cvaluated (nodal)
Mu4-Alribute Test Butery (MATS).
“Mubveratical Processing...
‘Oselomotor (FIT Workglace Safety Sereering) Evaluation
Physiological data rcording, i.
Profil of Mood Stas
Vinual Analog Seales
Side effets rating scale‘Simulater Si ois Quon (80),
light Simulator.
WAM (Wrist Activ Menor
Pravedce
Invprocessing.
General approac
General schedule for re-reerited pilots
General schedle for nen recruited pias,
Schedule for both groups of pilots
DATA ANALYSIS.
RESULTS
General Participant Cheactritcs.
Sleep Batimales.
Muli-Antebute Task Battery
Communications
Systems monitoring
Poel monitoring
Unstable wcking
-Mathematicel procersing
‘Reaction time for eottect responses.
Standard deviation of RI for corre! tempos.
‘Accuracy
Through
‘Oculomotor (FIT) data
Pupil diameter
Pupil consiriction amatitade
Pupil constriction latency.
Saocadiec velocity

Resting EEG data,
Delta activity
Theta acuity
Alpha setivity

Profile of Mood States.
Tension‘enaiety
Depressiam‘lgjection,
Angerhostlny
Vigoeactivay
Fotiguefivertia
Confusien-bessldorment.

Visual Analog Seale
Aleriness
Energy
Amiely.
Iiabilty
Jinteriness
‘Sleepiness.
Confidence
Talkativens§§v

To-fight fsinmlator) ERG,

‘Stoulator Flight Performance.
Srreighr climb.

Straight descent
Left 720 tam

Loft climbing tum
Le 360 tum

Right descending tum,
Right 360 tum
Steaight and lovels,

Composite Fight performance +

Simulator Sickness Questionnaire
Side Effects Questionnaire
DISCUSSION,
General Fatigue Effects
Efficacy of modafinil..
Cognitive effects
Physiological status,
Subjective raring
Simutater flight performance.
‘Modafinil side effects
SUMMARY AND CONCLUSIONS we BS

‘ACKNOWLEDGMENTS, vn . RR
REFERENCES se . 39
LIST OF FIGURES

Pay
Figure 1. Schematic of cach ofthe sleep deprivation tet eye... 28

Figure2_ The combined effets of reatueut condition an esting times on TO erors

uring the MATB communications task a
Figure 3. The effects of sleep deprivation (wih rearment condition cellapeed) on RT
(eft) and SDRT (right) during the MATB systems-r.onitaring wk a

Figure 4. ‘The effects of sleep deprivation (with treatment condition collapsed) or the
Gevintions of fuel ievels in tanks A and B during the MAT fuel-monitoring task...
FigurS, Theconbine effets of esimentcaon ad oing ine (Pah the

overt effect oftime on MATR tracking (ight). 4s
Figwe 6. The combined impact of eatatem condition and testing tine (lc) and the
‘overall offol of testing me (right) cm FIT pupil diameter. a

Figure 7, ‘The ovetll etfsc of sleep deprivation (testing timc) en FTT pupil constition
neney. ae
Figare 8, The combined impect of eatin? condition and testing time em FIT saccadic

velocity 49
Figure 9. ‘The imoractive effects of teatmers condition und eye closure on resting FPG.
delta activity at Cx and Paz SI

Figure 70, The overall condition main effects (modafinil vereus placebu} on esting Eo
delta acuivity at Cz, Pz, and Or.
Figure 11 Thc overal eflects of sleep deprivation (esting tne) on resting BEG deta

activity af Pz and O2... st
Figure 12. The infsracive sfftets of condition, testing time, and eye closare on resting
‘BEG theta activity at P 33

Figure "3. The combined fects of testing dine and eyes on resting BEG thote aetivty al
Fzand Or. 33
Figure 14. The combinod offcts of weuimen’ condition and testing tie on resting EEG
‘theta activity at Oz. 34
Figure 15. The oveeal eitects of ween! omaition (rmadadail versus placebo) on
resting EEG theta scivity al Cz, Pr, and Oz. si
igure 16. The effecis af time on resting EEG theta activity at Pz 24 O2 nnn
igure 17, The combined cffccta of testing time and eye on resting EEG alpha activity at
Cz and Pa. : i" 56
Figure 18. The marginaliy-signéficamt interactive effects of reatmnent com
closure ou resting EEG alpha activity 8¢ 02.
Figure 19. The interactive effets of woetment condiion and testing time on POMS

Uepression-dejetion tings nn 38
Tigare 20, The overal impact of teateneat condition Grodan] versus placebo} on
‘POWS unger-hostity ratings. a" 38
Figure 21. The separate impact of treatment conditinn (modafinil versus placebu) and

sleep deprivation (esting timc) 03 POMS vigor-activily ratings oe
Figure 22. The impact of sleep deprivation testing time) and condition ae POSES fatigue.
neta TaN nn - - st
Figure 23. The overall iespact af slesn deprivation (esting time) on POMS confusion.
bewilderment ratings. . nl
Figure 24, The effocis uf sleep deprivation (isting tite) on VAS alertness, energy,
jiteriness, sloepiness, confidence. and tlkativeness ratings, “a
Figuro 25. The independent effects of treatment condition and lestiog time on
performance of the st2ightclim® sn ; we os
Figure 26. Tke independent effecss of treatment condition and testing time 02
performance of the straight 465020 rnsnnnen rene 68
Figure 27. The interactive eifects of both treatment eonsiion and sheep depeivation on
performance of We left 720-degree ca. °

Figure 26, The indeperident impact of reafnicat conition (racdafn’l versus places) on
performance of the Jet climbing urn. ss ee
Figure 28. Tae non-significant pater of condition and tie effets on performance on

the left 360-deyree tam . — TD
Figure 30, The marginally-significant interactive efesis of weatment condition and deep
‘deprivation (testing time) on the performance ofthe right descending fur, 7

Figure 3). The overall impact af weatmnent condition (medafinil versus placcha) oa tbe

pperformaice of the right 360-deyree tam n
Figure 32. The overat] impact of treatment condition (modafinil versus placebo) onthe
performance ofthe stafght-and-level maneuvers a

Figure 33 The overall effects of weat-nont condition on tach maneuver (lef and tre
intersetive effects of yeatment condition and sleep deprivation across all raneuveze

combined (right) ‘ 74
Figure 34. The general impact of slosp deprivation (testing time) on visuomotor seates

‘eft) ond toral-liscomafor scores (ight) on the SSQ. . oS

LIST OF TARLES

Base

Table 1. Mewsured simolator Hight parameters an a eee)

Table 2, Flight maneavers, 7

“Table 3. Peremecters evaluated in each ofthe Aight mancuvers . 34

‘Table 4. Aye and Slight experience data forthe two groups. 39

Table 5. Actigraph-based estimules of sleep timss. 40

Table 6. Side effects reported under the mpdafinil und placebo eonditions, 76
BACKGROUND
US. superiority in eoday’s bare space in pat toms from our aiity to raintain
pressure the enemy by making them fight around Ie lock. By forcing our
adversaries to mrintin « 2-hour-day operational tempo, enemy eres wil ef fram
severe sleepiness leading to procedural ers, sloppy udment por planning, anda

general inability to act propery fo repilly changing situations. This provides a tactical

aalvanrago for the U.S. snd is part of the reason that the Air Foree Chief of StalT noted
that persistent and sustained operations, 24 hour a day, 7 days a week, are essential to

extabliching and malntaining superioriy in today’s combat environment (Elliot, 2001).

Simply forcing our enemies to perorr continuously without he benef of sufficient
daily sloop is very effective weapon in and ofits
“The Causes of Fatigue in Operational Conteus
‘Unfortunately, the conduct of eantnuous and sustained opcations cen pose
significant harurds 1 our own tops ifs area’ careful 1o property manage fatigne
among ourselves, Personnel and resource cutbacks within the U.S, Deparmmencof

Defense aver the past several yoars huvs resulted in force reductions of over 40 percent in

the Aumny Department of de Army, 1996) and inthe Air Fores (Congressional Rescaret
Service, 2002), wile the operations ter bas inereused hy as much es 40 pereent
(Comel, 1996). Needless to say. U.S. mlitry capes are increasingly sosined as
understaffed arts nrive to axcampiah more work with fewer resources. Some Fe! chat
this har rested in dnnished military smal eadiness (Spencer, 2008), in part

because of increased cognitive fatigue,
‘There is Tittle doubt that existing manpower consbainis have made it diffe! te

continously staf Uhe required work shifs with well-esled personnel around the clock.

Thus, prolonged werk bouts bave beeoms comune, sorter than-normal sleep periods.
unsvoidrbe, an fatigue Ro: bath ofthese factors tests ta meet operational
readiness (Dopantmant ofthe Amy, 1944), Tis well eetablshel hal eustained
‘Wakefitmess andthe resuking cumulative sleep debt inerease the Iheood that
personnel will briefly (and uncoainTbly) nod off on thajob, even durig demanding
tasks (Angus ang Hslograve, 1985). The longer personnel remit ake, the more
likely these sleep attacks” become, I adian, Meepiness aes heavy tol on resction
tine, motivation, atention, memory, endatance, and judgment ekrueger, 1991), Even in
peacetime, ovedy tired solders and aviators are tout ta he responsible for mumerows
Gsfgue-stated incideus an wecilensovery year (personal communication, 14Col
oomas Luna, US. Air Forge Safety Center, May, 2003)
“The Impact of Fatigue on Miliicy Performance

Although proaictions about the exac: eects of fli ae dfticut to ako. mos
researchers agree tha fitigns-telated performance and alertness decrements flow a
fairly reliable time conse. Canadian resstchers have posted that certain ments

abilities decline by about 30 percect after] nighl without sleep ar 6M percent after 2

nights without sleep (Angus, Piyeau, and Haslegtave, 1992), Seleutists at che Walter
ood Army Instivate of Research predict xaldios lose abuul 25 percent oftheit ability 10
perform useful mental work for every 24 hours. af eontinuons wake fulness eleuky' et

w, 1998). A recent Air Foree Research Laboratory study reveatod thal current, active:
duly Cightor pilots suffered Tiyht-performance doctines of 45 pereent below normal afer

(Caldvvell ef al, 2003).
Fatigue Remodics for Operational Settings

1c isa signifieart prablera in sustained military operations,

expecially nthe aviatnm selar whete a bigh level of vogitive perfomance is eesti
for safety and effectiveness, However, Frigue can be manaysd with scientifcaly-
validated countermescures. Sores ditferent strategies have een proposed for this
purpose
‘Nowhscmusolugical Satsrios

Fauphesiing oper worktest management is one sate thatthe lary bas
rightly focuseé upon for may years. However, when tho nica of combat reaches
a cetsn pont, it can be very dificult ta proporly cone sleep paris, ao thi ean lead
wo a substential problem with omthoob fatigue (Commun, 1997; Angus, Pigea and
Heslegrave, 1992), Even during peacctime, «recent survey of U.S. Army pilots revealed
that 26 percent conplsined of poor sep while inthe field or while travoling emay from
‘ur compared to only 5 percent comalaining of poor slasp al heir home post (Caldwell
tal, 2008), Slmilse difficulties are no-doubt resect in he US, Air onus, aldioug
sublished docunentation on this point is unavailable,

Snegie mp can help allovinte slep-deprvaron elated performance decrements
in situations where neps ae feasible (Dinges eta, 1988). However, scheduling maps is
nota staple mater in that opensional constants can male it very dilcatto ensue

‘proper control over nup timing (placsment of naps at optimal poins in tre sleep

deprivation period), nap duration (ensuring sufficient slp time), and nap scheduling,