Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis
(UC), are chronic relapsing diseases that carry considerable impact on patients' quality
of life, including objective measures such as increased bowel movements, bleeding and
fistulas and more subjective measures such as abdominal pain and fatigue.
While the pathogenesis of IBD is thought to result from a deregulated immune response
towards microbial antigens in genetically predisposed people, various associations
between environmental factors and disease activity have been described. Currently,
standard IBD treatment relies on immune modulating drugs. However, such drugs may cause
adverse effects, and up to 35% of patients show no response and up to 80% fail to achieve
remission.
The investigator would like to explore treating Crohn's disease with photobiomodulation
in the infrared (IR) range. Preliminary data suggest a positive effect of IR on Crohn's
disease activity, and would like to conduct a small scale, pilot clinical trial to
further clinically explore the safety and efficacy of this simple intervention.
Infrared is a safe, non-ionizing radiation spanning wavelengths from about 800 nanometers
(nm) to 1 millimeter (mm). The therapeutic effects of IR radiation were serendipitously
stumbled upon in the 1980s by NASA (National Aeronautics and Space Administration)
scientists who noticed improvement in skin lesions when assessing IR light for growing
potatoes in space. Since then, there has been a cautious advancement in assessing IR
therapy for various conditions and an increased understanding of some of the mechanisms
underlying its effect.
Alongside its beneficial effect, infrared treatment is not associated with serious
adverse effects in general and with relation to fertility in particular. In fact,
experimental data suggest that far IR (fIR) is safe for treating various medical
conditions including cancer, diabetes and female infertility.
Due to the documented effects of IR therapy on inflammation and its favorable safety
profile, the investigator would like to assess the efficacy of dose dependent response to
three intensities of fIR (low, medium and high) on Crohn's disease. A skilled staff
member will use a device emitting fIR radiation (8-10 microns) that is able to penetrate
deep into the body (up to at least 20 cm according to manufacturer). The device comprises
a heating pad that emits heat (up to 70 degree C) alongside fIR radiation.
Prior to treatment patient's bowel will be assessed by intestinal ultrasound (IUS) / CT/
MRI to determine the location of inflammation in order to focalize treatment, but also to
rule out the presence of abscess and cysts.
All patients will undergo 10 sessions of 30 minutes fIR therapy at the IBD clinic of the
Tel Aviv Medical Center (TLVMC) by a trained and qualified staff member. Each abdominal
quadrant will receive a similar amount of time of exposure to the IR, except for the
quadrant of the inflamed intestine (usually the right lower quadrant) which will be
exposed longer to the IR. During the treatment skin temperature will be recorded at 10
minutes intervals.
Patients responding to therapy (clinical response: ∆HBI≥3 and/or 50% reduction in
calprotectin), who did not achieve remission can continue for 10 more treatments.
Patients who are allocated to the control group will be eligible to transfer to the
experimental group after 10 sessions and receive 10 treatments with a medium intensity
fIR, providing the patient is not in remission.
After the completion of treatments, at week 11, bowel thickness will be assessed again by
IUS, as well as biochemical and clinical indexes.
Clinical score will be assessed using the Harvey-Bradshaw index (HBI) at weeks: 0, 5, and
10.
Stool will be collected at weeks 0, 5 and 10 for fecal calprotectin analysis and for
future microbiome/proteomics analysis.
Blood will be collected at weeks 0, 5, and 10 for C reactive protein (CRP), complete
blood count (CBC), liver function tests, creatinine and lipase. Serum will be frozen for
future proteomics and inflammatory measures analysis. Total blood volume will be less
than 20ml.
Patients will be asked to complete questionnaires evaluating their quality of life and
disease related symptoms and outcomes.
Side effects such as local skin thermal injury and blood tests abnormalities will be
documented. In case of local skin thermal injury, patients will be examined to determine
injury level, with recommendation to apply Aloe Vera paste and a follow-up call will be
made to document resolution of symptoms within 2 days.
Throughout the research period patients will be asked to maintain their usual lifestyle
with regards to nutrition and physical activity habits
Statistics Test results, clinical indices and side effects will be compared between
experimental and control groups as well as across the three treatment intensities, both
prior to and following treatment. These outcomes will also be analyzed within groups to
compare pre- and post-treatment results.
Patients in both groups will be categorized by disease severity level (according to HBI)
in order to correlate disease severity with treatment efficacy. Patients will be
randomized according to disease severity in order to keep an equal rate of patients with
mild clinical disease activity upon recruitment.
All statistical analyses will be performed using SPSS version 23.0 for Windows.
Demographic characteristics of the population will be described by mean±SD for continuous
variables, while categorical variables will be displayed as a frequency table.
Normal distribution will be tested by Kolmogorov-Smirnov test. If normality is rejected,
Due to the documented effects of IR therapy on inflammation and its favorable safety
profile, the investigator would like to assess the efficacy of dose dependent response to
three intensities of fIR (low, medium and high) on Crohn's disease. A skilled staff
member will use a device emitting fIR radiation (8-10 microns) that is able to penetrate
deep into the body (up to at least 20 cm according to manufacturer). The device comprises
a heating pad that emits heat (up to 70 degree C) alongside fIR radiation.

Prior to treatment patient's bowel will be assessed by intestinal ultrasound (IUS) / CT/
MRI to determine the location of inflammation in order to focalize treatment, but also to
rule out the presence of abscess and cysts.

All patients will undergo 10 sessions of 30 minutes fIR therapy at the IBD clinic of the
Tel Aviv Medical Center (TLVMC) by a trained and qualified staff member. Each abdominal
quadrant will receive a similar amount of time of exposure to the IR, except for the
quadrant of the inflamed intestine (usually the right lower quadrant) which will be
exposed longer to the IR. During the treatment skin temperature will be recorded at 10
minutes intervals.

Patients responding to therapy (clinical response: ∆HBI≥3 and/or 50% reduction in
calprotectin), who did not achieve remission can continue for 10 more treatments.
Patients who are allocated to the control group will be eligible to transfer to the
experimental group after 10 sessions and receive 10 treatments with a medium intensity
fIR, providing the patient is not in remission.

After the completion of treatments, at week 11, bowel thickness will be assessed again by
IUS, as well as biochemical and clinical indexes.

Clinical score will be assessed using the Harvey-Bradshaw index (HBI) at weeks: 0, 5, and
10.

Stool will be collected at weeks 0, 5 and 10 for fecal calprotectin analysis and for
future microbiome/proteomics analysis.

Blood will be collected at weeks 0, 5, and 10 for C reactive protein (CRP), complete
blood count (CBC), liver function tests, creatinine and lipase. Serum will be frozen for
future proteomics and inflammatory measures analysis. Total blood volume will be less
than 20ml.

Patients will be asked to complete questionnaires evaluating their quality of life and
disease related symptoms and outcomes.

Side effects such as local skin thermal injury and blood tests abnormalities will be
documented. In case of local skin thermal injury, patients will be examined to determine
injury level, with recommendation to apply Aloe Vera paste and a follow-up call will be
made to document resolution of symptoms within 2 days.

Throughout the research period patients will be asked to maintain their usual lifestyle
with regards to nutrition and physical activity habits

Statistics Test results, clinical indices and side effects will be compared between
experimental and control groups as well as across the three treatment intensities, both
prior to and following treatment. These outcomes will also be analyzed within groups to
compare pre- and post-treatment results.

Patients in both groups will be categorized by disease severity level (according to HBI)
in order to correlate disease severity with treatment efficacy. Patients will be
randomized according to disease severity in order to keep an equal rate of patients with
mild clinical disease activity upon recruitment.

All statistical analyses will be performed using SPSS version 23.0 for Windows.
Demographic characteristics of the population will be described by mean±SD for continuous
variables, while categorical variables will be displayed as a frequency table.

Normal distribution will be tested by Kolmogorov-Smirnov test. If normality is rejected,
non-parametric tests will be used.
