The Ambient Light Multiple Myeloma Study

Study Overview
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Brief Summary
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The aim of this multi-site randomized control trial will be is to assess the impact Systematic lighting on circadian rhythm entrainment, Inflammation, Neutropenic Fever and Symptom Burden among Multiple Myeloma Patients undergoing Autologous Stem Cell Transplantation. To achieve this aim, 200 multiple myeloma patients will receive one of two different light-treatments that are designed to promote circadian rhythm alignment. While receiving these light treatments, participants' sleep efficiency, urine melatonin levels, blood inflammatory cytokine levels and symptoms will be assessed over a 2-month period.

Detailed Description
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Individuals undergoing Autologous Stem Cell Transplant (ASCT) experience major transplant-related complications including elevated symptom burden, high rates of neutropenic fever, and increases in inflammatory cytokines. These transplant-related complications are augmented by circadian rhythms disruption (CRD), which leads to misalignment between melatonin levels and sleep times. Since light is a strong synchronizer of circadian rhythms, the proposed multi-site randomized controlled trial (RCT) will investigate whether lighting designed to deliver circadian effective light that promotes circadian alignment, will: 1) promote higher nighttime melatonin levels and better nighttime sleep, 2) reduce pro-inflammatory cytokines, 3) lower rates of neutropenic fever and 4) improve symptom burden in cancer patients undergoing Autologous Stem Cell Transplant. Hospital rooms for patients undergoing inpatient Autologous Stem Cell Transplant at the Mount Sinai Medical Center (MSMC) and at the Memorial Sloan Kettering Cancer Center (MSKCC)) will be retrofitted to install 1 of 2 lighting interventions, either circadian-effective (intervention) and circadian-ineffective (comparison) ambient light that may improve sleep. 1-2 weeks and no more than 2 months prior to transplant, participants will be given an Actiwatch, Daysimeter (personal light meter), sleep logs, questionnaires, and a urine collection kit to assess melatonin. One blood sample for cytokine analyses will be collected during one of the hospital visits prior to transplant. Blood draws are always done in the morning and always at a similar time for the same individual. The same outcomes (questionnaires, Actiwatch, Daysimeter, urine samples, blood samples) will be collected during transplant period and once, four weeks after engraftment.

Official Title
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Systematic Light Exposure Effects on Circadian Rhythms Entrainment, Inflammation, Neutropenic Fever and Symptom Burden Among Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Device: Circadian Effective Lighting
* Device: Circadian Ineffective Lightning (CIL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Multiple Myeloma diagnosis Scheduled to undergo their first Autologous Stem Cell Transplant procedure. 21years or older Able to provide informed consent. English-language proficient Exclusion Criteria: Previous Autologous Stem Cell Transplant procedure Pregnancy Eye diseases which limit the ability of light to be processed Secondary cancer diagnosis within the last 5 years Severe sleep disorders History of bipolar disorder or manic episodes Severe psychological impairment Previous use of light therapy Active infection including COVID-19 infection

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Circadian Effective Lighting (CEL)<br>The CEL will be performed in hospital sites over a 2-month period. | Device: Circadian Effective Lighting<br>* Participants will receive lighting with a spectrum of 300K, 500 lux to the eye level between 7:00am and 10:00am in the morning, and hospital lighting (<100lux) during the afternoon between 10:00am and 6:00pm. In the evening this group of participants will receive lighting with a spectrum of 3000K, <50lux at eye light level between 6:00PM and bedtime.<br>|
| Sham Comparator: Circadian Ineffective Lighting (CIL)<br>The comparator lighting will be performed identical to Arm 1, at specified lower levels of lighting. | Device: Circadian Ineffective Lightning (CIL)<br>* Participants will receive lower lighting levels in the morning (lighting with A spectrum of 300k, <50lux to the eye level between 7:00am and 10:00am) and the same lighting levels throughout the rest of the day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Urinary Melatonin | Participants will be given vials for collection and detailed instructions to void their bladders on AM rising and any prior nighttime voids starting 2 h prior to their normal bedtimes, at which time they will be asked to dim the lights down to a minimum and avoid using their self-luminous displays. Participants (and nurses) will collect each void during that overnight in a separate vial and to record the times of each voiding. Urinary melatonin-sulfate (6 sulfatoxymelatonin, aMT6s) measurements will be assayed using a commercially available ELISA kit (IBL International, Hamburg, Germany). | Baseline visit and 3 days after the Autologous Stem Cell Transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep Efficiency using Actigraphy at 7 days post-transplant | The participant will be asked to wear a wrist actigraph to monitoring sleep and activity, daily for 5 consecutive days. From the actigraphy data, change in sleep efficiency will be calculated. A higher sleep efficiency indicates improved sleep. | at 7 days post-transplant | 
| Sleep Efficiency using Actigraphy at 3 days after engraftment | The participant will be asked to wear a wrist actigraph to monitoring sleep and activity, daily for 5 consecutive days. From the actigraphy data, change in sleep efficiency will be calculated. A higher sleep efficiency indicates improved sleep. | at 3 days after engraftment | 
| Sleep Efficiency using Actigraphy at 4 weeks after engraftment | The participant will be asked to wear a wrist actigraph to monitoring sleep and activity, daily for 5 consecutive days. From the actigraphy data, change in sleep efficiency will be calculated. A higher sleep efficiency indicates improved sleep. | at 4 weeks after engraftment | 
| Inflammatory cytokine CRP levels at Baseline | A blood sample will be drawn to measure Inflammatory cytokine CRP levels. A decrease in CRP levels indicates reduced inflammation. | At baseline, or during the hospital visit prior to transplant | 
| Inflammatory cytokine CRP levels at 7 days following transplant | A blood sample will be drawn to measure Inflammatory cytokine CRP levels. A decrease in CRP levels indicates reduced inflammation. | at 7 days following transplant | 
| Inflammatory cytokine CRP levels at 3 days following engraftment | A blood sample will be drawn to measure Inflammatory cytokine CRP levels. A decrease in CRP levels indicates reduced inflammation. | at 3 days following engraftment | 
| Inflammatory cytokine CRP levels at 4 weeks following engraftment | A blood sample will be drawn to measure Inflammatory cytokine CRP levels. A decrease in CRP levels indicates reduced inflammation. | at 4 weeks following engraftment | 
| Number of Neutropenic Fevers at 7 days post-transplant | Physician notes on patient neutropenic fever will be obtained from medical records. Neutropenic fever will be defined as temperature of 38.2 C or higher and an absolute neutrophil count of less than 500 cells/mm. Physician notes are reviewed, and the number of times neutropenic fever is reported for each participant is recorded. | at 7 days post-transplant | 
| Number of Neutropenic Fevers at 3 days after engraftment | Physician notes on patient neutropenic fever will be obtained from medical records. Neutropenic fever will be defined as temperature of 38.2 C or higher and an absolute neutrophil count of less than 500 cells/mm. Physician notes are reviewed, and the number of times neutropenic fever is reported for each participant is recorded. | at 3 days after engraftment | 
| Number of Neutropenic Fevers at 4 weeks after engraftment | Physician notes on patient neutropenic fever will be obtained from medical records. Neutropenic fever will be defined as temperature of 38.2 C or higher and an absolute neutrophil count of less than 500 cells/mm. Physician notes are reviewed, and the number of times neutropenic fever is reported for each participant is recorded. | at 4 weeks after engraftment | 
| Circadian Light levels measured with Daysimeter (light monitor) at 7 days post-transplant | Participants will be asked to wear Daysimeters as a pendant or a pin during all waking times during the intervention weeks. Light measurements from Daysimeters used as pendants or pins are the closest to light measurements at eye level. The Daysimeter will also be used to monitor the total amount of circadian light received by the participant during the intervention weeks. | at 7 days post-transplant | 
| Circadian Light levels measured with Daysimeter (light monitor) at 3 days after engraftment | Participants will be asked to wear Daysimeters as a pendant or a pin during all waking times during the intervention weeks. Light measurements from Daysimeters used as pendants or pins are the closest to light measurements at eye level. The Daysimeter will also be used to monitor the total amount of circadian light received by the participant during the intervention weeks. | at 3 days after engraftment | 
| Circadian Light levels measured with Daysimeter (light monitor) at 4 weeks after engraftment | Participants will be asked to wear Daysimeters as a pendant or a pin during all waking times during the intervention weeks. Light measurements from Daysimeters used as pendants or pins are the closest to light measurements at eye level. The Daysimeter will also be used to monitor the total amount of circadian light received by the participant during the intervention weeks. | at 4 weeks after engraftment | 
| MD Anderson Symptom Inventory Score-Multiple Myeloma (MDASI-MM) at Baseline | MDASI-MM, with well-established reliability and validity, is 19-item measure of cancer-related symptom burden. It assesses 13 core symptoms common across cancer types and treatments (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness/tingling). In addition, 6 items assess symptom-related interference. All 19 items are rated with reference to the last 24 hours on a scale from 0 to 10 with anchors at the extreme ends of the scale (for symptom items, 0 = Not Present and 10 = As Bad As You Can Imagine; for interference items 0 = Did Not Interfere and 10 = Interfered Completely. Higher scores indicate higher symptom interference. The MDASI-Multiple Myeloma (MM) is the MDASI plus 7 additional items assessing symptoms specific to patients with MM (constipation, muscle weakness, diarrhea, sore mouth/throat, rash, difficulty concentrating and bone aches). | At baseline, or during the hospital visit prior to transplant | 
| MD Anderson Symptom Inventory Score-Multiple Myeloma (MDASI-MM) at 7 days following transplant | MDASI-MM, with well-established reliability and validity, is 19-item measure of cancer-related symptom burden. It assesses 13 core symptoms common across cancer types and treatments (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness/tingling). In addition, 6 items assess symptom-related interference. All 19 items are rated with reference to the last 24 hours on a scale from 0 to 10 with anchors at the extreme ends of the scale (for symptom items, 0 = Not Present and 10 = As Bad As You Can Imagine; for interference items 0 = Did Not Interfere and 10 = Interfered Completely. Higher scores indicate higher symptom interference. The MDASI-Multiple Myeloma (MM) is the MDASI plus 7 additional items assessing symptoms specific to patients with MM (constipation, muscle weakness, diarrhea, sore mouth/throat, rash, difficulty concentrating and bone aches). | at 7 days following transplant | 
| MD Anderson Symptom Inventory Score-Multiple Myeloma (MDASI-MM) at 3 days following engraftment | MDASI-MM, with well-established reliability and validity, is 19-item measure of cancer-related symptom burden. It assesses 13 core symptoms common across cancer types and treatments (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness/tingling). In addition, 6 items assess symptom-related interference. All 19 items are rated with reference to the last 24 hours on a scale from 0 to 10 with anchors at the extreme ends of the scale (for symptom items, 0 = Not Present and 10 = As Bad As You Can Imagine; for interference items 0 = Did Not Interfere and 10 = Interfered Completely. Higher scores indicate higher symptom interference. The MDASI-Multiple Myeloma (MM) is the MDASI plus 7 additional items assessing symptoms specific to patients with MM (constipation, muscle weakness, diarrhea, sore mouth/throat, rash, difficulty concentrating and bone aches). | at 3 days following engraftment | 
| MD Anderson Symptom Inventory Score-Multiple Myeloma (MDASI-MM) at 4 weeks following engraftment | MDASI-MM, with well-established reliability and validity, is 19-item measure of cancer-related symptom burden. It assesses 13 core symptoms common across cancer types and treatments (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness/tingling). In addition, 6 items assess symptom-related interference. All 19 items are rated with reference to the last 24 hours on a scale from 0 to 10 with anchors at the extreme ends of the scale (for symptom items, 0 = Not Present and 10 = As Bad As You Can Imagine; for interference items 0 = Did Not Interfere and 10 = Interfered Completely. Higher scores indicate higher symptom interference. The MDASI-Multiple Myeloma (MM) is the MDASI plus 7 additional items assessing symptoms specific to patients with MM (constipation, muscle weakness, diarrhea, sore mouth/throat, rash, difficulty concentrating and bone aches). | at 4 weeks following engraftment | 
| Perceived Stress Scale Score at Baseline | Perceived Stress Scale is a 10-item self-report questionnaire that measures a person's self-reported evaluation of their perception of stressfulness in a situation over the past 1 month of their lives. It assesses a person's feelings and thoughts over a 1-month period. Participants rate each item on a 4-point scale (0 = never, 1 = almost never, 2 = sometimes, 3 = fairly often, 4 = often) producing scores ranging from 0-40. Scores are obtained by reversing the scores on items 4,5,7 and 8 like so: 0=1,1=3,2=2,3=1,4=0, and then adding up the scores for each item to obtain a total score. Higher scores indicate greater stress. | At baseline, or during the hospital visit prior to transplant | 
| Perceived Stress Scale Score at 7 days post-transplant | Perceived Stress Scale is a 10-item self-report questionnaire that measures a person's self-reported evaluation of their perception of stressfulness in a situation over the past 1 month of their lives. It assesses a person's feelings and thoughts over a 1-month period. Participants rate each item on a 4-point scale (0 = never, 1 = almost never, 2 = sometimes, 3 = fairly often, 4 = often) producing scores ranging from 0-40. Scores are obtained by reversing the scores on items 4,5,7 and 8 like so: 0=1,1=3,2=2,3=1,4=0, and then adding up the scores for each item to obtain a total score. Higher scores indicate greater stress. | at 7 days post-transplant | 
| Perceived Stress Scale Score at 3 days following engraftment | Perceived Stress Scale is a 10-item self-report questionnaire that measures a person's self-reported evaluation of their perception of stressfulness in a situation over the past 1 month of their lives. It assesses a person's feelings and thoughts over a 1-month period. Participants rate each item on a 4-point scale (0 = never, 1 = almost never, 2 = sometimes, 3 = fairly often, 4 = often) producing scores ranging from 0-40. Scores are obtained by reversing the scores on items 4,5,7 and 8 like so: 0=1,1=3,2=2,3=1,4=0, and then adding up the scores for each item to obtain a total score. Higher scores indicate greater stress. | at 3 days following engraftment | 
| Perceived Stress Scale Score at 4 weeks following engraftment | Perceived Stress Scale is a 10-item self-report questionnaire that measures a person's self-reported evaluation of their perception of stressfulness in a situation over the past 1 month of their lives. It assesses a person's feelings and thoughts over a 1-month period. Participants rate each item on a 4-point scale (0 = never, 1 = almost never, 2 = sometimes, 3 = fairly often, 4 = often) producing scores ranging from 0-40. Scores are obtained by reversing the scores on items 4,5,7 and 8 like so: 0=1,1=3,2=2,3=1,4=0, and then adding up the scores for each item to obtain a total score. Higher scores indicate greater stress. | at 4 weeks following engraftment | 
| Patient-Reported Outcomes Measurement Information System -Sleep Disturbance Short Form (PROMIS-SD) Score at Baseline | Participants will complete the 8-item PROMIS Sleep Disturbance Short Form (PROMIS-SD) during assessment periods to assess the pure domain of sleep disturbances among adults ages 18 and older. Participants rate each item on a 5-point scale (1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always), producing scores ranging from 8-40. Raw scores for the 8 items are summed for a global score; higher scores indicate greater severity of sleep disturbance. | At baseline, or during the hospital visit prior to transplant | 
| Patient-Reported Outcomes Measurement Information System -Sleep Disturbance Short Form (PROMIS-SD) Score at 7 days post-engraftment | Participants will complete the 8-item PROMIS Sleep Disturbance Short Form (PROMIS-SD) during assessment periods to assess the pure domain of sleep disturbances among adults ages 18 and older. Participants rate each item on a 5-point scale (1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always), producing scores ranging from 8-40. Raw scores for the 8 items are summed for a global score; higher scores indicate greater severity of sleep disturbance. | at 7 days following transplant | 
| Patient-Reported Outcomes Measurement Information System -Sleep Disturbance Short Form (PROMIS-SD) Score at 3 days following engraftment | Participants will complete the 8-item PROMIS Sleep Disturbance Short Form (PROMIS-SD) during assessment periods to assess the pure domain of sleep disturbances among adults ages 18 and older. Participants rate each item on a 5-point scale (1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always), producing scores ranging from 8-40. Raw scores for the 8 items are summed for a global score; higher scores indicate greater severity of sleep disturbance. | at 3 days following engraftment | 
| Patient-Reported Outcomes Measurement Information System -Sleep Disturbance Short Form (PROMIS-SD) Score at 4 weeks following engraftment | Participants will complete the 8-item PROMIS Sleep Disturbance Short Form (PROMIS-SD) during assessment periods to assess the pure domain of sleep disturbances among adults ages 18 and older. Participants rate each item on a 5-point scale (1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always), producing scores ranging from 8-40. Raw scores for the 8 items are summed for a global score; higher scores indicate greater severity of sleep disturbance. | at 4 weeks following engraftment | 
| Patient-Reported Outcomes Measurement Information System (PROMIS)- Fatigue Score at Baseline | Participants, 18 years and older, will complete the 13-item PROMIS Fatigue Short Form items which asses a range of self-reported symptoms of fatigue from mild feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that decreases one's ability to execute daily activities and function normally in family or social roles. On the form, Participant Fatigue is divided by the impact of fatigue on physical, mental, and social activities. All items assess fatigue over the past 7 days. Participants will rate each item on a 5-point scale (1= Not at all, 2= A little bit, 3= Somewhat, 4= Quite a bit, 5= Very much). Scores will be summed to produce a total or raw score ranging from 8. (lowest score) to 40, with a higher score indicating more frequent fatigue. If all questions were responded to, a scoring table will be used to generate the T-score. | At baseline, or during the hospital visit prior to transplant | 
| Patient-Reported Outcomes Measurement Information System (PROMIS)- Fatigue Score at 7 days following transplant | Participants, 18 years and older, will complete the 13-item PROMIS Fatigue Short Form items which asses a range of self-reported symptoms of fatigue from mild feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that decreases one's ability to execute daily activities and function normally in family or social roles. On the form, Participant Fatigue is divided by the impact of fatigue on physical, mental, and social activities. All items assess fatigue over the past 7 days. Participants will rate each item on a 5-point scale (1= Not at all, 2= A little bit, 3= Somewhat, 4= Quite a bit, 5= Very much). Scores will be summed to produce a total or raw score ranging from 8. (lowest score) to 40, with a higher score indicating more frequent fatigue. If all questions were responded to, a scoring table will be used to generate the T-score. | at 7 days following transplant | 
| Patient-Reported Outcomes Measurement Information System (PROMIS)- Fatigue Score at 3 days following engraftment | Participants, 18 years and older, will complete the 13-item PROMIS Fatigue Short Form items which asses a range of self-reported symptoms of fatigue from mild feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that decreases one's ability to execute daily activities and function normally in family or social roles. On the form, Participant Fatigue is divided by the impact of fatigue on physical, mental, and social activities. All items assess fatigue over the past 7 days. Participants will rate each item on a 5-point scale (1= Not at all, 2= A little bit, 3= Somewhat, 4= Quite a bit, 5= Very much). Scores will be summed to produce a total or raw score ranging from 8. (lowest score) to 40, with a higher score indicating more frequent fatigue. If all questions were responded to, a scoring table will be used to generate the T-score. | at 3 days following engraftment | 
| Patient-Reported Outcomes Measurement Information System (PROMIS)- Fatigue Score at 4 weeks following engraftment | Participants, 18 years and older, will complete the 13-item PROMIS Fatigue Short Form items which asses a range of self-reported symptoms of fatigue from mild feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that decreases one's ability to execute daily activities and function normally in family or social roles. On the form, Participant Fatigue is divided by the impact of fatigue on physical, mental, and social activities. All items assess fatigue over the past 7 days. Participants will rate each item on a 5-point scale (1= Not at all, 2= A little bit, 3= Somewhat, 4= Quite a bit, 5= Very much). Scores will be summed to produce a total or raw score ranging from 8. (lowest score) to 40, with a higher score indicating more frequent fatigue. If all questions were responded to, a scoring table will be used to generate the T-score. | at 4 weeks following engraftment |