The objective of the study is to determine whether exposure to the SpectraMax light therapy device, emitting light in a combined spectra of blue/green light (460 * 570 nm) with an intensity of approximately 1300 Lux, will be more effective in…
ID
Source
Brief title
Condition
- Other condition
- Movement disorders (incl parkinsonism)
- Mood disorders and disturbances NEC
Synonym
Health condition
angststoornissen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary effectiveness endpoint is the change in the MDS-UPDRS (Movement
Disorders Society * Unified Parkinson*s Disease Rating Scale) composite score
of sections II and III at Treatment Visit 3 (after six months of treatment).
Secondary outcome
1. Change of the scores on Parts I, II, III, IV and of the total MDS UPDRS.
2. Change of the score on the Beck Depression Inventory (BDI-II)
3. Change of the score on the Beck Anxiety Inventory (BAI)
4. Change of the three sub domain and total scores on the Parkinson*s
Disease Sleep Scale-2 (PDSS 2)
5. Change of the score on the Epworth Sleepiness Scale (ESS)
6. Change of the eight sub-scales and total scores on the Parkinson's
Disease Questionnaire (PDQ-39)
7. Change of the Clinical Global Impression - Severity Index (CGI-S),
Efficacy Index (CGI-E) and final Global Improvement (CGI-I) score.
8. Change of the score on column 1, column 2 and combined total of the
Wearing-Off Questionnaire (Q10)
The following data will be collected and analyzed separately from the primary
and secondary endpoint data for exploratory research purposes and will be
reported separately from the Investigation Final Report:
9. Elbow-to-Fist (ETA) and Floor-to-Knee (FTK) Timed Motor
Tests
10. Improvement of sleep latency, total sleep time, and number
and frequency of awakenings as measured by actigraphy
Background summary
Idiopathic Parkinson*s Disease and Circadian Function:
Parkinson*s disease (PD) is traditionally described as a neurodegenerative
disorder affecting the dopamine (DA) function in the nigro-striatal dopamine
(NSD) system, giving rise to the characteristic motor symptoms of rigidity,
bradykinesia, and tremor. The neurodegenerative process is not limited to the
NSD system, but affects other systems as well [1] and many PD patients
experience a range of non-motor symptoms, comprising cognitive, mood and sleep
disturbances [1, 2]. The motor symptoms, as well as the non-motor symptoms,
have a negative impact on quality of life and daily functioning in PD patients
[3-6].
Treatment of PD is mainly based on dopamine replacement in the form of the DA
precursor L-dopa or DA agonists. Unfortunately, not all symptoms respond to
dopaminergic treatment, and the efficacy of these agents decreases as the
disease progresses [7]. Moreover, L-dopa and DA agonists can induce
side-effects, such as response fluctuations and dyskinesias [7]. Therefore,
research on alternative treatment strategies for the motor and non-motor
symptoms of PD is imperative.
Research on the circadian system has demonstrated that a misalignment of the
circadian rhythm can induce depressive symptoms and sleep disturbances [8, 9].
In PD, there is a frequent co-occurrence of sleep disturbances and depressive
symptoms [10, 11]. This points to a dysfunction of the circadian system as a
common underlying factor. The center of the circadian system is the circadian
*pacemaker*, which is located in the suprachiasmatic nucleus (SCN) of the
hypothalamus. Its endogenous rhythm is slightly different from the 24-hour
day-night cycle and has to be entrained by signals (or *zeitgebers*) such as
light, activity and food [12]. Light provides the *daytime* signal, by exciting
specialized melanopsin containing ganglion cells in the retina, that project
towards the SCN via the retino-hypothalamic tract [8]. The output signals of
the SCN convey circadian timing information to brain areas regulating behavior,
body temperature, autonomic and neuroendocrine systems, including the secretion
of melatonin by the pineal gland [8]. The secretion of melatonin is inhibited
by the SCN during the light cycle, but the SCN also contains melatonin
receptors that inhibit SCN firing, thereby creating a negative feedback loop
[13, 14].
Circadian malfunction is suggested to play an important role in the development
and progression of PD [15]. The balance between melatonin and dopamine, which
sit in functional opposition to regulate day/night activities, appears to have
an important role in this process [16]. In an animal model of PD, motor
dysfunction was exacerbated by administration of exogenous melatonin [17]. In
another study, intravitreal injection of very small amounts of L-dopa or a
melatonin antagonist improved motor function in rats with experimentally
induced PD, suggesting involvement of the retina [18]. In PD patients treated
with L-dopa, a phase-advanced circadian rhythm was observed compared to healthy
controls and de novo PD patients [19-21]. The influence of circadian
malfunction on the frequently occurring sleep-wake disturbances in PD has
recently been studied in an experimental model of PD in non-human primates
[22]. The results of this study suggest that DA depletion of the NSD system
prevents the circadian system to effectively drive rhythmic locomotor rest-wake
activity [22].
The circadian system appears to play a key role in PD, and might therefore
provide an important starting point for an alternative treatment for this
disease. Bright light therapy (BLT) acts as a strong zeitgeber and can restore
circadian rhythmicity [23, 24]. BLT might therefore be able to exert positive
effects on both the motor and nonmotor symptoms in PD patients.
Study Background:
This study aims at evaluating the safety and efficacy of a non-invasive BLT
device to be used with ongoing dopaminergic treatment for PD.
The positive effects on BLT in PD have been studied in both preclinical and
clinical research. In an experimental model of PD in rats, exposure to constant
light significantly improved motor function [17]. In PD patients, the effects
of BLT have been evaluated in several pilot studies and one retrospective, open
label study [16, 25-27]. These studies demonstrated that BLT for PD patients
might have a positive effect on motor function, sleep disorders and mood [16,
25-27]. However, a randomized, placebo-controlled trial on the effects of BLT
in PD patients is still lacking.
In the past, BLT studies employed broad bandwidth, polychromatic light at high
intensities (10,000 + lux). Recent research has demonstrated that exposure to
narrow-band blue light is more potent in melatonin suppression than longer
wavelength light [28]. In PD patients, who have a phase-advanced circadian
rhythm,[19-21] blue light might be more effective in restoring circadian rhythm
than polychromatic light [29]. Unpublished, pilot data from PD patients
suggests that while blue light produces improvement, green light may yield
further benefits [30, 31]. The high intensity of 10,000 Lux of previously used
BLT produces glare and can induce side effects such as headaches, nausea,
jitteriness, or eyestrain.[32] Optimizing the bandwidth of light may not only
improve the efficacy of BLT, but also allow a reduction of the intensity of the
light administered, decreasing side effects [32]. Therefore, this study will
investigate the effectiveness of light that produces the majority of its energy
in the medium wavelength frequencies (~460 * 570 nm), at an intensity of 1300
Lux.
Study objective
The objective of the study is to determine whether exposure to the SpectraMax
light therapy device, emitting light in a combined spectra of blue/green light
(460 * 570 nm) with an intensity of approximately 1300 Lux, will be more
effective in reducing the primary motor and non-motor symptoms of PD, than a
placebo device that emits polychromatic light with an intensity of 100 Lux.
This study embraces the latest development in circadian function and
phototherapy in an attempt to determine the potential efficacy of light therapy
in treating PD.
Study design
Dit betreft een multicenter, gerandomiseerde, placebo-gecontroleerde studie..
De studie wordt verdeeld in drie perioden: screening, behandeling en follow-up.
Na de formele screening zal er een baseline-meting van twee weken zijn, die
wordt gevolgd door een behandelingsperiode van zes maanden. Aan het einde van
de behandelperiode wordt de lamp geretourneerd. Eén maand later zal de
deelnemer terugkomen voor een follow-up meting.
De screening vindt plaats bij het eerste polikliniek bezoek. Deelnemers krijgen
aansluitend een baseline-meting. Zij krijgen hierbij een slaapdagboek en
actimeter voor een baseline-meting van hun slaap en activiteit gedurende twee
weken. Aan het einde van deze baseline-meting zal de onderzoekscoördinator op
huisbezoek gaan om de actiwatch en het slaapdagboek op te halen. Patiënt die de
meting hebben volgens afspraak hebben volbracht zullen gerandomiseerd worden
naar de experimentele of controlegroep. De onderzoekscoördinator zal de
lichttherapie-lamp installeren en de deelnemer instrueren de lamp één maal
daags in de avond gedurende een uur te gebruiken conform de verstrekte
instructies.
De behandelperiode duurt 6 maanden. Meting van primaire motorische en
niet-motorische symptomen vindt plaats bij de baseline-meting en op Maand 1, 3
en 6 Behandelbezoek (of eerder, bij een bezoek na vroegtijdige beëindiging van
de studie), en bij het Follow-upt bezoek na zeven maanden. Het slaapdagboek en
de actigrafie worden herhaald in de twee weken voor het Behandelbezoek van
Maand 3 en 6.
In totaal vinden er dus vijf polikliniek-bezoeken plaats: één screenings- en
baseline-meting, drie behandelmetingen en één follow-up meting (zie tabel 2 en
3 van het protocol). Voor alle metingen geldt dat patiënten gezien worden in de
ochtend. Gedurende de onderzoeksperiode zal een standaard speling van +/- vijf
dagen toegestaan worden voor het plannen van metingen. De onderzoekscoördinator
zal twee keer per maand telefonisch contact hebben met de deelnemers tot de
zesde maand. Alle afspraken zullen plaatsvinden in de ochtend. Bij afname van
de UPDRS wordt rekening gehouden met het medicatieschema van de dopaminerge
medicatie; niet eerder dan 1 uur na de laatste dosis, en niet later dan 1 uur
vóór de volgende geplande dosis.
Intervention
The Spectramax* light therapy device is an artificial light source with a
combined spectrum of blue/green light (460 * 570 nm) at an irradiance of
approximately 400 µW/cm2. The control light therapy device is identical in
appearance to the Spectramax* light device, but it emits a broad bandwidth
polychromatic light of approximately 50 µW/cm2 (100 lux). Participants will be
exposed to the light source for 1 hour daily for 6 months.
Study burden and risks
At the irradiance levels emitted by commonly utilized light therapy devices,
dermatologic safety concerns are minimal. The Spectramax light therapy lamp is
certified to Risk Group 0 indicating no photobiological risk as per the
international standard, IEC 62471:2006. Similarly, thermal damage to cornea,
lens or retina requires milliwatt-to-watt exposure, far in excess of that
emitted from these therapeutic devices. While these devices emit less than
2,000 lux, ocular safety for 6,000 lux white fluorescent sources has been
assessed and comprehensive optometric examinations of individuals with healthy
eyes who used white-light therapy daily during fall/winter months for up to 5
years did not reveal adverse effects (Gallin et al., 1995; Gorman et al.,
1993). The control and blue-green light LED sources to be utilized in the
present research have been determined to have an averaged radiance well below
the 10-mW/cm2*sr safety limit for continuous viewing (see Appendix for Sliney
reports).
Over the last 25 years, light therapy with bright fluorescent light, and LED
light therapy have been tested in many individuals and serious irreversible
adverse effects have not been reported. The most common side effect of light
therapy is irritability or agitation that remits after termination of the light
or decrease of the daily duration of exposure. Participants will be carefully
monitored for such side effects and light therapy exposure will be decreased or
eliminated if these adverse effects occur.
Written instructions will be given, potential adverse effects will be
discussed, and subjects will be instructed to telephone the study site with any
questions or should any adverse effects occur. The Investigator shall withdraw
any subject where continued involvement in the investigation may negatively
affect the subject*s safety or welfare.
6222 West 10480 North
Highland UT 84003
US
6222 West 10480 North
Highland UT 84003
US
Listed location countries
Age
Inclusion criteria
1. Males and females, with Stage II * IV, Idiopathic Parkinson*s Disease, as assessed by Hoehn-Yahr Scale
2. On optimized, stable dopamine replacement therapy for at least 1 month
Exclusion criteria
1. Subjects younger than 45 years old.
2. Participation in a study of investigational or marketed drugs or devices during the 30-day period prior to the start of the study or during the study
3. Subjects who are medically complicated, medically unstable and/or have other severe co-morbid disease states, as determined by the investigator.
4. History of concurrent psychiatric illness that would preclude compliance with the protocol and/or ability to complete the study safely
5. History or current diagnosis of major psychiatric disorder including Bipolar I Disorder that could interfere with accurate assessment and effective treatment
6. Beck Depression Inventory score of greater than or equal to 14
7. Patients on stable anti-depressant dose for less than 6 weeks
8. An anticipated need for dopamine therapy change for the duration of the trial
9. Less than one month of stopping an anti-depressant or psychoactive medication
10. History of current or recent (within previous 12 months) alcohol, narcotic or other drug abuse by DSM-5 criteria
11. Active suicidal or homicidal ideation or plan as determined by the Investigator, or a score of 2 or higher item 9 of the BDI-II.
12. Previous use of light therapy treatment
13. Females of childbearing age, e.i. capable of becoming pregnant
14. Night shift work within the past 6 months, or planned during the investigation
15. Planned travel for more than two weeks outside of two time zones from the state in which the trial is being conducted
16. Planned travel outside of two time zones from home during the last two months of the Subject*s involvement in the Investigation
17. Current use or use within the previous 1 month of photosensitizing or other medications that in the opinion of the investigator would interfere with the safety of the subject during the trial including:
a. amiodarone,
b. benoxaprofen,
c. chlorpromazine,
d. demeclocycline,
e. fleroxacin,
f. nalidixic acid,
g. ofloxacin,
h. piroxicam,
i. porfimer,
j. psoralens,
k. quinidine,
l. temoporfin tetracycline,
m. oral isoretinoin (Accutane),
n. St. John*s wort,
o. melatonin.
18. History of significant eye trauma or disease, retinopathy, and/or cataract of a level that would significantly affect transmission or processing of light through either eye
19. Other neurological disorders that in the opinion of the investigator would interfere with the conduct of the study
20. Pre-existing major joint problems that in the opinion of the investigator would interfere with subject compliance
21. History of cerebral insult or central nervous system infection that in the opinion of the Investigator would preclude successful participation in Investigation related procedures.
22. Cognitive impairment, e.g. as determined by the Montreal Cognitive Assessment, that in the opinion of the Investigator would interfere with the conduct of the Investigation.
23. Focal neurological deficits that in the opinion of the Investigator would interfere with the conduct of the Investigation.
24. High Total Drug Burden or severe dyskinesia attributable to dopamine replacement therapy that would preclude successful participation in the Investigation related procedures or interventions in the opinion of the site Investigator. Total Drug Burden is defined as the total of the L-dopa equivalents, plus peripheral decarboxylase inhibitor, of each medication in the patient*s drug therapy.
25. Subjects who refuse to sign written informed consent or give approval for notification of the subject*s personal physician of their interest to participate in the investigation.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL46350.029.14 |