To Decrease Fatigue With Light Therapy

Study Overview
=================
Brief Summary
-----------------
Cancer related fatigue (CRF) is one of the most prevalent and distressing long-term complaints reported by (non-) Hodgkin survivors. The SPARKLE study will test the efficacy of two intensities of light therapy on cancer related fatigue. Additionally, it explores possible working mechanisms of light therapy on CRF including improvements in sleep quality, psychosocial variables (depression, anxiety, cognitive complaints, and quality of life), and changes in biological circadian rhythms.

Detailed Description
-----------------
Rationale: Cancer related fatigue (CRF) is one of the most prevalent and distressing long-term complaints reported by (non-)Hodgkin survivors. So far, there is no standard treatment. Some non-pharmacological interventions have shown large effects but show limitations as well, e.g. they are labor intensive. A novel and promising treatment for CRF is exposure to bright white light (BWL) therapy. This low-cost intervention is easy to deliver and has a low burden for professionals as well as for patients. Objective: To examine the efficacy of BWL therapy as an intervention for CRF. As a secondary aim, this study will explore possible working mechanisms including changes in sleep quality, psychological variables, biological circadian rhythms, sleep-wake cycles, inflammation markers and genotype. Study design: A multicenter randomized controlled trial will invite participants and allocate them to either a light intensity 1 condition (n=80) or a light intensity 2 condition (n=80). The longitudinal design will include four measurement points: baseline, mid-intervention, post-intervention, and at 3 and 9 months follow-up. Study population: Hodgkin and diffuse large B-cell lymphoma (DLBCL) survivors fulfilling the clinical criteria of CRF and a survivorship of ≥ 3 years will be invited. Fatigue should not be attributable to a clear somatic cause or treatment for secondary cancer in the past year. Moreover, 25 Hodgkin survivors without CRF will be recruited to explore the association between circadian rhythms and CRF. Intervention: The light intervention includes exposure to light for 30 minutes within the first half hour after awakening during 3,5 weeks. Main study parameters/endpoints: The main study parameter in this study is the change in CRF from baseline to post-intervention and at 3 and 9 months follow-up. This will be assessed with the Multidimensional Fatigue Inventory. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation in this study includes completion of a light intervention for 3,5 weeks (30 min each day) and 2 visits (1h) to the treating hospital pre- and post-intervention. The visits aim to provide instructions and equipment and to collect two blood samples. Additionally, 5 saliva samples will be collected by the participant at home pre- and post-intervention. Moreover, participants complete questionnaires (30 min, 4 times) and wear an accelerometer (10d, 4 times and during light therapy) to objectively measure sleep quality and activity. Risks of the light intervention are limited, although there are few known reports of agitation, headache and nausea during the first days of light exposure. Benefits are the use of an easy to administer treatment for one of the most distressing symptoms that participants report.

Official Title
-----------------
Improving Sleep Quality, Psychosocial Functioning, and Cancer Related Fatigue With Light Therapy

Conditions
-----------------
Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma

Intervention / Treatment
-----------------
* Device: Light therapy intensity 1
* Device: Light therapy intensity 2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A history of Hodgkin or DLBCL with a survivorship of ≥ 3 years. The presence of moderate to severe fatigue symptoms since diagnosis of or treatment for Hodgkin lymphoma or DLBCL. Exclusion Criteria: Fatigue is explained by a somatic factor as defined in the guidelines of chronic fatigue syndrome of the Dutch internists association (NIV). When a somatic cause for fatigue is resolved by stable medication use ≥ 6 months, patients can be included in the current trial. Pregnancy (until 3 months postnatal) or women who provide breast feeding Extensive surgical operations in the past 3 months. Current diagnosis of a psychiatric disorder (e.g. personality disorders, psychosis, bipolar disorder) which would limit participation. Diagnosis of and treatment for a secondary malignancy in the past 12 months. Presence of photophobia (abnormal intolerance to visual perception of light) or another eye disease that shows symptoms of photophobia (e.g. aniridia, retinitis pigmentosa, glaucoma). Current or previous use of light therapy for more than 1 week. Current employment in shift work. Insufficient knowledge of the Dutch language.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Light intensity 1<br>The light intervention includes exposure to white light (10.000 lux) at a distance of 45 cm for 30 minutes within the first half hour after awakening during 3 weeks and 4 days. This can be done while engaged in other activities, for example reading the newspaper or eating breakfast. | Device: Light therapy intensity 1<br>* Exposure to white light (10.000 lux) in the morning<br>|
| Experimental: Light intensity 2<br>The light intervention includes exposure to white light (10-20 lux) at a distance of 45 cm for 30 minutes within the first half hour after awakening during 3 weeks and 4 days. This can be done while engaged in other activities, for example reading the newspaper or eating breakfast. | Device: Light therapy intensity 2<br>* Exposure to white light (10-20 lux) in the morning<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer related fatigue | Fatigue is assessed with the Multidimensional Fatigue Inventory | Change from baseline fatigue at end of 3,5 weeks light therapy | 
| Cancer related fatigue | Fatigue is assessed with the Multidimensional Fatigue | Change from baseline fatigue at 3 months after light therapy | 
| Cancer related fatigue | Fatigue is assessed with the Multidimensional Fatigue | Change from baseline fatigue at 9 months after light therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective sleep quality | Subjective sleep quality is assessed with the Pittsburg Sleep Quality Index | Change from baseline subjective sleep quality at end of 3,5 weeks light therapy | 
| Subjective sleep quality | Subjective sleep quality is assessed with the Pittsburg Sleep Quality Index | Change from baseline subjective sleep quality at 3 months after light therapy | 
| Subjective sleep quality | Subjective sleep quality is assessed with the Pittsburg Sleep Quality Index | Change from baseline subjective sleep quality at 9 months after light therapy | 
| Objective sleep quality | Objective sleep quality data is assessed by wearing an accelerometer for 10 days | Change from baseline objective sleep quality at end of 3,5 weeks light therapy | 
| Objective sleep quality | Objective sleep quality data is assessed by wearing an accelerometer for 10 days | Change from baseline objective sleep quality at 3 months after light therapy | 
| Objective sleep quality | Objective sleep quality data is assessed by wearing an accelerometer for 10 days | Change from baseline objective sleep quality at 9 months after light therapy | 
| Depression | Depression is assessed with the Center for Epidemiological Studies - depression scale | Change from baseline depression at end of 3,5 weeks light therapy | 
| Depression | Depression is assessed with the Center for Epidemiological Studies - depression scale | Change from baseline depression at 3 months after light therapy | 
| Depression | Depression is assessed with the Center for Epidemiological Studies - depression scale | Change from baseline depression at 9 months after light therapy | 
| Anxiety | Anxiety is assessed with the State Trait Anxiety Inventory-6 items | Change from baseline anxiety at end of 3,5 weeks light therapy | 
| Anxiety | Anxiety is assessed with the State Trait Anxiety Inventory-6 items | Change from baseline anxiety at 3 months after light therapy | 
| Anxiety | Anxiety is assessed with the State Trait Anxiety Inventory-6 items | Change from baseline anxiety at 9 months after light therapy | 
| Quality of life | Quality of life is assessed with the Medical Outcome studies short form (SF-36) | Change from baseline quality of life at end of 3,5 weeks light therapy | 
| Quality of life | Quality of life is assessed with the Medical Outcome studies short form (SF-36) | Change from baseline quality of life at 3 months after light therapy | 
| Quality of life | Quality of life is assessed with the Medical Outcome studies short form (SF-36) | Change from baseline quality of life at 9 months after light therapy | 
| Subjective cognitive complaints | Subjective cognitive complaints assessed with the Medical Outcomes Studies Cognitive functioning. | Change from baseline subjective cognitive complaints at end of 3,5 weeks light therapy | 
| Subjective cognitive complaints | Subjective cognitive complaints assessed with the MD Anderson Symptom Inventory | Change from baseline subjective cognitive complaints at end of 3,5 weeks light therapy | 
| Subjective cognitive complaints | Subjective cognitive complaints assessed with the Medical Outcomes Studies Cognitive functioning | Change from baseline subjective cognitive complaints at 3 months after light therapy | 
| Subjective cognitive complaints | Subjective cognitive complaints assessed with the MD Anderson Symptom Inventory | Change from baseline subjective cognitive complaints at 3 months after light therapy | 
| Subjective cognitive complaints | Subjective cognitive complaints assessed with the Medical Outcomes Studies Cognitive functioning | Change from baseline subjective cognitive complaints at 9 months after light therapy | 
| Subjective cognitive complaints | Subjective cognitive complaints assessed with the MD Anderson Symptom Inventory | Change from baseline subjective cognitive complaints at 9 months after light therapy | 
| Objective cognitive complaints - alertness and sustained attention | Objective cognitive complaints are assessed with the Psychomotor Vigilance Task. | Change from baseline objective cognitive complaints at end of 3,5 weeks light therapy | 
| Objective cognitive complaints - long-term memory | Objective cognitive complaints are assessed with the 15 words test. | Change from baseline objective cognitive complaints at end of 3,5 weeks light therapy | 
| Objective cognitive complaints - short-term memory | Objective cognitive complaints are assessed with the digit span task. | Change from baseline objective cognitive complaints at end of 3,5 weeks light therapy | 
| Cancer worries | Cancer worries is assessed with the Cancer Worry scale | Change from baseline cancer worries at end of 3,5 weeks light therapy | 
| Cancer worries | Cancer worries is assessed with the Cancer Worry scale | Change from baseline cancer worries at 3 months after light therapy | 
| Cancer worries | Cancer worries is assessed with the Cancer Worry scale | Change from baseline cancer worries at 9 months after light therapy | 
| Fatigue catastrophizing | Fatigue catastrophizing is assessed with the Fatigue catastrophizing scale | Baseline | 
| Self-efficacy | Self-efficacy is assessed with the Self-efficacy Scale 28 | Baseline | 
| Circadian rhythms of cortisol and melatonin | Circadian rhythms of cortisol and melatonin will be determined from saliva samples | Change from baseline circadian rhythms at end of 3,5 weeks light therapy | 
| Biomarkers of inflammation and genotype | Biomarkers of inflammation (hsIL-6, sTNF-RII, IL-1RA, hsCRP, vitamin D) and genotype will be determined from blood samples | Change from baseline levels of biomarkers at end of 3,5 weeks light therapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
light therapy, cancer related fatigue, sleep quality, biological rhythms