Mea­sur­ing Re­al-World Sleep with Actig­ra­phy: Three Clin­i­cal Tri­al Use Cas­es

Dis­turbed or im­paired sleep has been the sub­ject of in­creased re­search at­ten­tion in re­cent years, as both a pri­ma­ry dis­or­der and in cas­es where dis­turbed sleep is a symp­tom of an­oth­er dis­ease. Dis­turbed sleep is com­mon in peo­ple with arthri­tis, atopic der­mati­tis, Alzheimer’s Dis­ease, Parkin­son’s Dis­ease, and many oth­er con­di­tions. Re­search is fo­cused on mea­sur­ing and di­ag­nos­ing these sleep dis­or­ders, as well as the de­vel­op­ment of new treat­ments to im­prove sleep across a broad range of in­di­ca­tions. Wear­able de­vices pro­vide a low-bur­den and re­mote ap­proach to ob­jec­tive­ly quan­ti­fy peo­ple’s sleep in their re­al life, of­ten re­veal­ing mean­ing­ful in­sights that might not be avail­able with polysomnog­ra­phy or self-re­port da­ta. While sleep ar­chi­tec­ture and sleep stag­ing are dif­fi­cult to es­ti­mate with ac­celerom­e­try alone, actig­ra­phy is sen­si­tive to treat­ment ef­fects in pre­vi­ous stud­ies of sleep dis­or­ders.¹

Use Case 1: Mea­sur­ing Sleep in Rheuma­toid Arthri­tis

More than 80% of peo­ple with rheuma­toid arthri­tis (RA) re­port fa­tigue as part of their symp­toms.² While most in­ter­ven­tions are fo­cused on re­duc­tion in pain, im­paired sleep is an im­por­tant in­di­ca­tor of dis­ease sever­i­ty and treat­ment ef­fect. In stud­ies with pri­ma­ry pain end­points, actig­ra­phy-de­rived sleep end­points can help more ful­ly char­ac­ter­ize the par­tic­i­pant’s ex­pe­ri­ence. With con­tin­u­ous day and night wear pe­ri­ods, ad­di­tion­al dai­ly mea­sures of phys­i­cal ac­tiv­i­ty can al­so be mea­sured.

• In pre­vi­ous stud­ies of rheuma­toid arthri­tis, Acti­Graph de­vices have shown high sen­si­tiv­i­ty and speci­fici­ty for clas­si­fi­ca­tion of seden­tary time, light in­ten­si­ty, and mod­er­ate in­ten­si­ty phys­i­cal ac­tiv­i­ty.³
• In a cur­rent Phase 2 glob­al RA tri­al, an Acti­Graph Cen­tre­Point In­sight Watch is be­ing used to mea­sure to­tal sleep time (TST), wake af­ter sleep on­set (WA­SO), and dai­ly step counts as ex­plorato­ry mea­sures.

Use Case 2: De­tect­ing Im­paired Sleep in Peo­ple with Neu­rode­gen­er­a­tive Dis­eases

Cog­ni­tive and func­tion­al de­cline are typ­i­cal end­points in neu­rode­gen­er­a­tive dis­or­ders. Sleep dis­tur­bances are the sec­ond most fre­quent non-mo­tor com­plaints among peo­ple with Parkin­son’s dis­ease.⁴ Those with Alzheimer’s Dis­ease have a high­er preva­lence of sleep dis­or­ders and be­hav­ioral dis­tur­bances than healthy el­der­ly adults.⁵ Actig­ra­phy has been shown to be an ap­pro­pri­ate method to ex­am­ine sleep dis­or­ders in de­men­tia pa­tients.⁶ Past stud­ies have shown cor­re­la­tion be­tween actig­ra­phy mea­sures can be valid pre­dic­tors of tau pathol­o­gy with po­ten­tial clin­i­cal use.⁷

• Actig­ra­phy-de­rived sleep mea­sures de­tect­ed sig­nif­i­cant treat­ment re­spons­es to a nov­el brain stim­u­la­tion ther­a­py in a re­cent PhI/II RCT study, cor­rob­o­rat­ing im­prove­ments in Ac­tiv­i­ty of Dai­ly Liv­ing.⁸
• Walk­ing speed and stride length have both been shown to be im­pact­ed in pa­tients with de­men­tia.⁹ With con­tin­u­ous day and night wear pe­ri­ods, ad­di­tion­al mea­sures of gait and walk­ing speed can al­so be col­lect­ed.
• In a re­cent Phase 2 glob­al study of pa­tients with de­men­tia, re­searchers used an Acti­Graph GT9X to track move­ment counts dur­ing sleep.

Use Case 3: As­sess­ing Treat­ment Ef­fi­ca­cy in Chron­ic In­som­nia

One of the most com­mon sleep dis­or­ders is in­som­nia, char­ac­ter­ized by the re­cur­ring dif­fi­cul­ty to fall or re­main asleep de­spite mo­ti­va­tion and means to do so. Most adults ex­pe­ri­ence in­som­nia at some point of their lives, but when peo­ple ex­hib­it symp­toms at least three times per week for at least three months, in­som­nia is con­sid­ered a chron­ic con­di­tion and clin­i­cal in­ter­ven­tions might be nec­es­sary.

• The Acti­Graph GT9X was used in a re­cent Ph2 study to as­sess the ef­fi­ca­cy of med­i­c­i­nal cannabis on treat­ing chron­ic in­som­nia.¹⁰ Actig­ra­phy mea­sures of to­tal sleep time and sleep ef­fi­cien­cy de­tect­ed sig­nif­i­cant and sub­stan­tial im­prove­ments as­so­ci­at­ed with the treat­ment, cor­rob­o­rat­ing self-re­port­ed sleep di­ary. On the oth­er hand, polysomnog­ra­phy did not de­tect treat­ment ef­fects, po­ten­tial­ly due to the in­fre­quen­cy and lab­o­ra­to­ry set­up of the as­sess­ments.

Com­pli­ance

Past stud­ies have re­port­ed good com­pli­ance when us­ing Acti­Graph de­vices for col­lect­ing sleep mea­sures in clin­i­cal tri­als. Par­tic­i­pant com­pli­ance as high as 95% has been shown with wrist-worn de­vice da­ta col­lec­tion wear pe­ri­ods.¹¹ Acti­Graph de­vices are easy to use, and every site and par­tic­i­pant is trained on how to op­er­ate the de­vice dur­ing a tri­al. Cen­ter­Point, Acti­Graph’s soft­ware ecosys­tem, al­lows for near re­al-time mon­i­tor­ing of com­pli­ance and wear pe­ri­ods.

End-to-End Da­ta Trans­paren­cy

Acti­Graph’s ful­ly trans­par­ent sys­tem re­lies on proven, open-source al­go­rithms de­vel­oped by the sci­en­tif­ic com­mu­ni­ty to gen­er­ate mean­ing­ful, re­li­able mea­sures. Full ac­cess to “fu­ture-proof” raw sen­sor da­ta means that new and more so­phis­ti­cat­ed sleep al­go­rithms and analy­sis tech­niques can be ap­plied to col­lect­ed da­ta as they emerge. Tri­al spon­sors are able main­tain da­ta com­pa­ra­bil­i­ty across phas­es and stud­ies and de­rive the high­est qual­i­ty out­comes, now and in the fu­ture.

Ex­pe­ri­ence

The Acti­Graph plat­form has been used to mea­sure sleep in dozens of in­di­ca­tions across a broad range of ther­a­peu­tic ar­eas. Acti­Graph de­vices have been used to mea­sure sleep end­points in more than 50 Phase 2 and Phase 3 in­dus­try-spon­sored clin­i­cal tri­als since 2015.

Are you in­ter­est­ed in learn­ing more about how actig­ra­phy-de­rived sleep mea­sures can en­hance your clin­i­cal de­vel­op­ment pro­gram? Con­tact us to speak with a mem­ber of our team.

Ref­er­ences: 

1. Zeitzer, Jamie M et al. “Ef­fect of Su­vorex­ant vs Place­bo on To­tal Day­time Sleep Hours in Shift Work­ers: A Ran­dom­ized Clin­i­cal Tri­al.” JA­MA net­work open vol. 3,6 e206614. 1 Jun. 2020, doi:10.1001/ja­manet­workopen.2020.6614
2. Arthri­tis Foun­da­tion. https://www.arthri­tis.org
3. O’Brien, Cia­ra M et al. “Mea­sure­ment of seden­tary time and phys­i­cal ac­tiv­i­ty in rheuma­toid arthri­tis: an Acti­Graph and ac­tiv­PALt­m­val­i­da­tion study.” Rheuma­tol­ogy in­ter­na­tion­al vol. 40,9 (2020): 1509-1518. doi:10.1007/s00296-020- 04608-2
4. Lod­do, Giuseppe et al.“The Treat­ment of Sleep Dis­or­ders in Parkin­son’s Dis­ease: From Re­search to Clin­i­cal Prac­tice.” Fron­tiers in neu­rol­o­gy vol. 8 42. 16 Feb. 2017, doi:10.3389/fneur.2017.00042
5. Zhou, Guoyu MD, PhD; Liu, Shuang­wu MD; Yu, Xi­aolin MD; Zhao, Xin­jin MD; Ma, Lin MD; Shan, Peiyan MD, High preva­lence of sleep dis­or­ders and be­hav­ioral and psy­cho­log­i­cal symp­toms of de­men­tia in late-on­set Alzheimer dis­ease, Med­i­cine: De­cem­ber 2019 – Vol­ume 98 – Is­sue 50 – p e18405
6. Brzec­ka, An­na et al. “Sleep Dis­or­ders As­so­ci­at­ed With Alzheimer’s Dis­ease: A Per­spec­tive.” Fron­tiers in neu­ro­science vol. 12 330. 31 May. 2018, doi:10.3389/fnins.2018.00330
7. López-Gar­cía, Sara et al. “Sleep Time Es­ti­mat­ed by an Actig­ra­phy Watch Cor­re­lates With CSF Tau in Cog­ni­tive­ly Unim­paired El­ders: The Mod­u­la­to­ry Role of APOE.” Fron­tiers in ag­ing neu­ro­science vol. 13 663446. 2 Aug. 2021, doi:10.3389/fna­gi.2021.663446
8. Cimenser, A. et al. Sen­so­ry-Evoked 40-Hz Gam­ma Os­cil­la­tion Im­proves Sleep and Dai­ly Liv­ing Ac­tiv­i­ties in Alzheimer’s Dis­ease Pa­tients. Front. Syst. Neu­rosci. 15, 746859 (2021).
9. Beauchet, Olivi­er et al. “Gait analy­sis in de­ment­ed sub­jects: In­ter­ests and per­spec­tives.” Neu­ropsy­chi­atric dis­ease and treat­ment vol. 4,1 (2008): 155-60. doi:10.2147/ndt.s2070
10. Jen­nifer H Walsh, Kath­leen J Mad­di­son, Tim Rankin, Kevin Mur­ray, Nigel McAr­dle, Melis­sa J Ree, David R Hill­man, Pe­ter R East­wood, Treat­ing in­som­nia symp­toms with med­i­c­i­nal cannabis: a ran­dom­ized, crossover tri­al of the ef­fi­ca­cy of a cannabi­noid med­i­cine com­pared with place­bo, Sleep, Vol­ume 44, Is­sue 11, No­vem­ber 2021, zsab149, https://doi.org/10.1093/sleep/zsab149
11. Mel­by, Ka­trine et al. “Actig­ra­phy as­sess­ment of mo­tor ac­tiv­i­ty and sleep in pa­tients with al­co­hol with­draw­al syn­drome and the ef­fects of in­tranasal oxy­tocin.” PloS one vol. 15,2 e0228700. 13 Feb. 2020, doi:10.1371/jour­nal. pone.0228700