None listed
Conditions
Brief summary
While the cause of amyotrophic lateral sclerosis (ALS) is unknown, recent evidence points to an important role for immune dysregulation in ALS disease. In particular, a role for the suppressive arm of the immune system, directed primarily by regulatory T cells (Tregs), may slow disease progression. In this project we will conduct the first trial in ALS of a specific immune therapy, narrow band UVB phototherapy, known to increase Treg activity. Narrow band UVB phototherapy is a simple, safe and non-invasive treatment used routinely to suppress damaging immune reactions in other conditions such as psoriasis. We will determine whether UVB phototherapy is safe in ALS and whether it induces regulatory T cells. If effective, this would support a larger trial examining whether UVB phototherapy can slow the progression of disease. Slowing disease progression using phototherapy would be a major advance for this disease. If phototherapy has no effect on disease progression but can increase regulatory T cells it may be useful in combination with other neuron-regenerating treatments that are in development, by reducing immune-mediated neuron damage. The study proposed here will expand our knowledge of the role of the immune system in ALS and highlight the potential to harness its regulatory arm to slow disease progress.
Interventions
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
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.
Sponsors
Western Sydney Local Health District
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
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.
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.
Outcome results
None listed