Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000802505
Ethics application status
Approved
Date submitted
21/07/2015
Date registered
3/08/2015
Date last updated
7/06/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Narrow band ultraviolet B (UVB) phototherapy in amyotrophic lateral sclerosis
Scientific title
A Phase IIA trial in amyotrophic lateral sclerosis of the safety and biological efficacy (increase in regulatory T cells) of narrow-band UVB phototherapy plus standard-of-care compared to standard-of-care only.
Secondary ID [1] 287128 0
nil
Universal Trial Number (UTN)
U1111-1172-3494
Trial acronym
PhotoNeurone
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 295665 0
Condition category
Condition code
Neurological 295943 295943 0 0
Neurodegenerative diseases
Inflammatory and Immune System 296001 296001 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Standard care plus Intervention
Intervention: Phototherapy using a Waldmann UV7002 (TL01) phototherapy cabinet with output (between wavelengths 311-312 nm) of 0.6 mW/cm2 will be used. Eye protection will be with a full face mask. Phototherapy will be given three times/week for twelve weeks (36 exposures in total). Phototherapy will be delivered according to the patient’s skin type using the psoriasis protocol recommended by Waldmann. The starting dose of 0.1 - 0.4 J/cm2 will be based on the skin type and will be well below the likely erythema threshold. All patients will receive 20% increments on their initial dose, up to a maximal dose of 2.0 - 3.0 J/cm2 dependent upon skin type, similar to that previously published (Paul et al, (2012) J Eur Acad Dermatol Venereol, 26 Suppl 3, 1-10). At each visit the dose will be given and any adverse effects will be recorded. The time of each UVB exposure varies from approximately 1 to approximately 4 minutes, with increasing lengths of exposure over time on therapy as the skin becomes tanned.

Patient calendars, reminder phonecalls and free dedicated parking at the hospital will be provided to improve adherence to the intervention.

Arm 2: Standard care.
Intervention code [1] 292379 0
Treatment: Devices
Comparator / control treatment
Standard care.
This includes riluzole medication plus multidisciplinary care.
Control group
Active

Outcomes
Primary outcome [1] 295621 0
Safety as assessed by adverse events assessments and clinical assessments.

Adverse events with NB-UVB therapy are very rare as this is a well-established therapy used to treat dermatological conditions for more than 20 years, but the possible side-effects of treatment are as follows:

1. The most common side-effect is sunburn (significant redness or pain following the treatment). It is common for the skin to become slightly red after treatment. Rarely blisters can occur.

2. Some patients could develop a skin rash in response to phototherapy, as the treatment may uncover a previously unknown sun sensitive skin condition.

3. There is a theoretically increased risk of skin cancers similar to going out in the sun. Short term treatments such as this one do not seem to entail any more sunlight hazard than a similar amount of sun exposure.

Adverse events will be assessed 3 times per week at the time of phototherapy treatment by interview and physical examination by the phototherapy nurse.

Neurological adverse events are not expected, however neurological assessments will be conducted using the ALS Functional Rating Scale-Revised at months 3, 6 and 12.

Dermatological assessments will be conducted by study dermatologist at the completion of phototherapy and at 12 months by physical examination.
Timepoint [1] 295621 0
Adverse events assessments conducted throughout the 12 months of the study.
Clinical assessments conducted at months 3, 6 and 12.
Primary outcome [2] 295622 0
Change from baseline in CD4+CD25+FoxP3+CD127lo regulatory T cells as a proportion of all leukocytes. This will be assessed by dual-platform analysis using full blood count and flow cytometry of peripheral blood mononuclear cells.
Timepoint [2] 295622 0
Timepoint will be selected as that with the highest mean change from baseline compared to the standard of care only group from all timepoints measured: months 1, 3, 6, 9 and 12.
Secondary outcome [1] 316022 0
Serum 25-hydroxyvitamin-D(3) levels
Timepoint [1] 316022 0
Timepoint will be selected as that with the highest mean compared to the standard of care only group from all timepoints measured: months 1, 3, 6, 9 and 12.

Eligibility
Key inclusion criteria
1. Possible, probable or definite sporadic or familial ALS using the Awaji criteria (de Carvahlo et al, 2008, Clin neurophysiol, 119: 497-503).
2. Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) of greater than or equal to 38.
3. Ability to comply with all study procedures including standing in the treatment cubicle, attending 36 phototherapy visits, blood collection, and clinical assessments.

Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. ALS symptoms, other cardiovascular/ respiratory disease or any condition that prevents standing in the enclosed treatment cubicle for up to 10 min.
2. Any immunological conditions including autoimmunity or other inflammatory conditions, or immunosuppressive or immunomodulatory medication that may independently influence regulatory T cell numbers.
3. Pregnancy or planning to become pregnant, as this alters regulatory T cell numbers.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subjects prescreened as potentially meeting study criteria from clinic of PI will be invited to consider the study and given the Participant Information and Consent Form. Upon signing of informed consent subjects will be screened by study clinician to determine whether they meet study criteria. If so they will be enrolled. Randomisation will occur from opaque envelopes containing equal numbers of assignments each to "phototherapy" and to "no phototherapy".
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
We will calculate the change in regulatory T cells (Treg) as % leukocytes from baseline for each individual, and determine the difference between % Treg change from baseline for treated and untreated patients using t-test or Mann-Whitney U test as appropriate. We conducted sample size calculations using empirical means and standard deviations of normalised change on narrow-band-UVB phototherapy data from a group of treated individuals and 7 untreated controls showing a significant difference between the groups (now published; Schweintzger N et al including CI Byrne , Br J Dermatol. 2015 May 30. doi: 10.1111/bjd.13930), and required a sample size of 10 in each group to achieve 80% power to detect p<0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/08/2015
Actual
6/08/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4071 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 10019 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 291686 0
Charities/Societies/Foundations
Name [1] 291686 0
Motor Neurone Disease Research Institute of Australia
Country [1] 291686 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District
Address
Research Governance Office, Westmead Hospital, Cnr Hawkesbury & Darcy Roads, Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 290362 0
None
Name [1] 290362 0
Address [1] 290362 0
Country [1] 290362 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293214 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 293214 0
Ethics committee country [1] 293214 0
Australia
Date submitted for ethics approval [1] 293214 0
Approval date [1] 293214 0
01/05/2015
Ethics approval number [1] 293214 0
(4219) AU RED HREC/15/WMEAD/71

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58930 0
Prof Steve Vucic
Address 58930 0
Department of Neurology,
Westmead Hospital,
Cnr Hawkesbury & Darcy Roads
Westmead, NSW, 2145
Country 58930 0
Australia
Phone 58930 0
+61 2 9845 8738
Fax 58930 0
Email 58930 0
[email protected]
Contact person for public queries
Name 58931 0
Fiona McKay
Address 58931 0
Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, 176 Hawkesbury Rd, Westmead, NSW, 2145
Country 58931 0
Australia
Phone 58931 0
+61 2 8627 3603
Fax 58931 0
Email 58931 0
[email protected]
Contact person for scientific queries
Name 58932 0
Steve Vucic
Address 58932 0
Department of Neurology,
Westmead Hospital,
Cnr Hawkesbury & Darcy Roads,
Westmead, NSW, 2145
Country 58932 0
Australia
Phone 58932 0
+61 2 9845 8738
Fax 58932 0
Email 58932 0
[email protected]

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