Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Extracorporeal Photopheresis of Patients With Crohn's Disease Using 5-aminolevulinic Acid

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04164849
Recruitment Status : Recruiting
First Posted : November 15, 2019
Last Update Posted : December 10, 2019
Sponsor:
Collaborator:
Oslo University Hospital
Information provided by (Responsible Party):
Jørgen Jahnsen, University Hospital, Akershus

Brief Summary:
In the clinical trial the investigators will assess efficacy, safety and tolerability after single and multiple doses of 3 millimolar 5 aminolevulinic acid (Gliolan®) in combination with blue-light (405 nanometer) photopheresis in patients with active crohns disease. The study is a proof-of-concept pilot with 10 included patients where every patient will get active treatment. The use of 5-aminolevulinic acid in combination with blue-light photopheresis is a first-in-human trial. Primary endpoints include clinical response and adverse events (safety). Secondary endpoints include endoscopic improvement, quality of life questionnaires, faecal calprotectin, C-reactive protein and mechanisms of action (differences in t-cells and other cells before and after treatment). All patients will get treatment every 2 weeks for 10 weeks (6 treatments-induction) with evaluation at week 13. If any effect on week 13 eligible for study extension with treatment every 4 weeks for up to 12 months. Through the study the investigators will see if this kind of photopheresis is safe and can be an option for a larger randomized-controlled-trial. In addition the investigators will see if photopheresis as an option can be further developed for other diseases as well (ie other T-cell mediated diseases or patients already receiving photopheresis as a treatment).

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: 5-aminolevulinic acid Procedure: Blue light photopheresis Procedure: Transfusion Procedure: Continuous Mononuclear Cell Collection (CMNC) Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: A combined phase 1/2 pilot study with emphasize on safety/tolerability but also clinical efficacy/effect
Masking: None (Open Label)
Masking Description: all patients will receive active treatment
Primary Purpose: Treatment
Official Title: Extracorporeal Photopheresis of Patients With Crohn's Disease Using 5-aminolevulinic Acid
Actual Study Start Date : November 22, 2019
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : February 28, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: 5-ALA photopheresis
All patients will receive 5-aminolevulinic acid (5-ALA) in combination with blue light photopheresis. The investigators will collect mononuclear cells by connecting patient to Spectra Optia with CMNC (continuous mononuclear cell collection protocol), and these cells will include active T-lymphocytes. 5-ALA will be incubated for 1 hour to produce photoactive protoporphyrin-IX (PpIX) before light exposure.
Drug: 5-aminolevulinic acid
5-aminolevulinic acid (30 mg/ml) will be added to mononuclear cells in a dose of 3 millimolar and incubated for 1 hour

Procedure: Blue light photopheresis
The mononuclear cells incubated with 5-aminolevulinic acid for 1 hour will be exposed to blue light.

Procedure: Transfusion
The treated cells are transferred back to the patient as a standard blood transfusion

Procedure: Continuous Mononuclear Cell Collection (CMNC)
The mononuclear cells are collected using the Spectra Optia with the Continuous Mononuclear Cell Collection protocol. 90 ml of mononuclear cells will be collected and 100 ml of 0,9% saline will be added to dilute the cells before incubation with drug and photopheresis.




Primary Outcome Measures :
  1. Clinical response [ Time Frame: Week 13, 26 (28 for patients not eligible for study extension), 38, 50, 64 and 3 months after last treatment ]
    Clinical response (Harvey Bradshaw Index change > 3 from baseline or less than 4 points)

  2. Safety and tolerability adverse events [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Frequency, seriousness and intensity of adverse events

  3. Safety and tolerability Electrocardiogram-PR interval [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in PR interval before and after treatment

  4. Safety and tolerability Electrocardiogram-PR segment [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in PR segment before and after treatment

  5. Safety and tolerability Electrocardiogram-QT interval [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in QT interval before and after treatment

  6. Safety and tolerability Electrocardiogram-ST segment [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in ST segment before and after treatment

  7. Safety and tolerability Electrocardiogram-T wave [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in T wave before and after treatment

  8. Safety and tolerability Electrocardiogram-QRS complex [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in QRS complex before and after treatment

  9. Safety and tolerability vital signs [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Vital signs (heart rate) before and after treatment

  10. Safety and tolerability blood pressure [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Vital signs (systolic and diastolic blood pressure) before and after treatment

  11. Alkaline phosphatase [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in serum alkaline phosphatase (U/L) before and after treatment

  12. Aspartate transferase [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in serum aspartate transferase(U/L) before and after treatment

  13. Alanine aminotransferase [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in serum alanine aminotransferase (U/L) before and after treatment

  14. Albumin [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Albumin (g/L) before and after treatment

  15. Bilirubin [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Bilirubin (micromol/L) before and after treatment

  16. Gamma glutamyltransferase [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum gamma glutamyltransferase (U/L) before and after treatment

  17. White cell count [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood White cell count (10^9/L) before and after treatment

  18. Neutrophil granulocytes [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood neutrophil granulocytes (10^9/L) before and after treatment

  19. Lymphocytes [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood Lymphocytes (10^9/L) before and after treatment

  20. Monocytes [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood Monocytes (10^9/L) before and after treatment

  21. Eosinophile granulocytes [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood Eosinophile granulocytes (10^9/L) before and after treatment

  22. Basophile granulocytes [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood Basophile granulocytes (10^9/L) before and after treatment

  23. Platelet count [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood Platelet count (10^9/L) before and after treatment

  24. Mean Cell Volume [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood Mean Cell Volume (fL) before and after treatment

  25. Mean Cell hemoglobin [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood Mean Cell hemoglobin (picogram) before and after treatment

  26. International Normalized Ratio [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood International Normalized Ratio (0,8-1,2) before and after treatment

  27. Hemoglobin [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Blood Hemoglobin (g/dL) before and after treatment

  28. Calcium [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Calcium (millimol/L) before and after treatment

  29. Potassium [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Potassium (millimol/L) before and after treatment

  30. Sodium [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Sodium (millimol/L) before and after treatment

  31. Creatinin [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Creatinine (micromol/L) before and after treatment

  32. Lactate Dehydrogenase [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Lactate Dehydrogenase (U/L) before and after treatment

  33. Cholesterol [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Cholesterol (millimol/L) before and after treatment

  34. Total Protein [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Total Protein (g/L) before and after treatment

  35. Carbamide [ Time Frame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension) in addition to week 64 and 3 months after last treatment. ]
    Changes in Serum Carbamide (millimol/L) before and after treatment


Secondary Outcome Measures :
  1. CD4+ and CD8+ T cell subpopulations [ Time Frame: Week 0, 10 and 50 ]
    Number of CD4+ and CD8+ T cell subpopulations before and after treatment assessed by flow cytometry.

  2. Apoptosis and necrosis [ Time Frame: Week 0, 10 and 50 ]
    Number of cells in apoptosis or necrosis before and after treatment assessed by flow cytometry

  3. Clinical remission [ Time Frame: Week 13 and/or sustained/delayed response in week 26 (28 for patients not eligible for study extension), 38, 50, 64 and 3 months after last treatment. ]
    Harvey Bradshaw Index < 5 points

  4. Endoscopic efficacy [ Time Frame: Week 13 and 64 with baseline visit as reference. ]
    Simple Endoscopic Score for Crohns Disease >49 % improvement or < 3 (endoscopic remission)

  5. Faecal calprotectin [ Time Frame: Week 13, 26 (28 for patients not eligible for study extension), 38, 50, 64 and/or 3 months after last treatment ]
    Change from baseline

  6. Concentration of C reactive protein in blood [ Time Frame: Week 13, 26 (28 for patients not eligible for study extension), 38, 50, 64 and/or 3 months after last treatment ]
    Change from baseline

  7. Quality of life questionnaire Short-Form 36 (SF-36) [ Time Frame: Week 13, 26 (28 for patients not eligible for study extension), 38, 50, 64 and/or 3 months after last treatment ]
    Change of both total and subscores of SF-36 from baseline. Min 0 Max 100. Higher value is better quality of life.

  8. Quality of life questionnaire Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Week 13, 26 (28 for patients not eligible for study extension), 38, 50, 64 and/or 3 months after last treatment ]
    Change of both total and subscores of IBDQ from baseline. Min 32 Max 224. Higher value is better quality of life.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of informed consent
  2. Age above 18
  3. Male or female patient with active Crohn's disease (6)
  4. Women of childbearing potential (WOCBP) will have to use highly effective methods of contraception throughout the entire study.
  5. Inadequate response (a) or intolerance to biological therapy

    a. Inadequate response on ongoing treatment is defined as: i. Progressive disease: increasing Harvey Bradshaw Index/Calprotectin/Simple Endoscopic Score for Crohns Disease and/or worsening of radiologic images after 6 months.

    ii. Stable disease: no-response after 6 months

  6. Active inflammation in the gut documented by

    1. Harvey Bradshaw Index >5 and
    2. Endoscopy with Simple Endoscopic Score for Crohns Disease equal to or above 6 points or equal to or above 4 points if only isolated ileitis is present and/or
    3. Inflammatory marker; fecal calprotectin > 250 and/or C reactive protein > 5

Exclusion Criteria:

  1. Photosensitive comorbidities, porphyria or known hypersensitivity to 5-aminolevulinic acid or porphyrins
  2. Patients with aphakia
  3. Pregnant or breast-feeding women. A negative urine pregnancy test must be demonstrated in female patients of child-bearing potential at the Screening Visit and before every treatment.
  4. Ongoing cardiac and pulmonary diseases or aspartate transaminase alanine aminotransferase, Bilirubin or International Normalized Ratio value ≥ 3x upper limit of normal or clinically significant electrocardiogram findings
  5. Subjects with polyneuropathy
  6. Uncontrolled infection or fever
  7. History of heparin-induced thrombocytopenia, absolute neutrophil count <1x109, platelet count <20x10 9
  8. Body weight below 40 kg
  9. Investigator considers subject unlikely to comply with study procedures, restrictions and requirements.
  10. Presence of other gastrointestinal diseases potentially influencing the study endpoints
  11. History of any clinically significant disease or disorder which in the opinion of the investigator, may either put the patient at risk because of participation in the study, or influence the result or the patient's ability to participate in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04164849


Contacts
Layout table for location contacts
Contact: Jørgen Jahnsen, PhD +4767966013 jorgen.jahnsen@medisin.uio.no

Locations
Layout table for location information
Norway
Akershus University Hospital Recruiting
Lorenskog, Akershus, Norway, 1478
Contact: Jorgen Jahnsen, PhD       jorgen.jahnsen@medisin.uio.no   
Contact: Kristian Espeland, Md       kristian.espeland@ahus.no   
Sponsors and Collaborators
University Hospital, Akershus
Oslo University Hospital
Layout table for additonal information
Responsible Party: Jørgen Jahnsen, Professor, University Hospital, Akershus
ClinicalTrials.gov Identifier: NCT04164849    
Other Study ID Numbers: twostepala
First Posted: November 15, 2019    Key Record Dates
Last Update Posted: December 10, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jørgen Jahnsen, University Hospital, Akershus:
Crohns Disease
Photopheresis
5-aminolevulinic acid
Gliolan
UVA-PIT
Additional relevant MeSH terms:
Layout table for MeSH terms
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Aminolevulinic Acid
Photosensitizing Agents
Dermatologic Agents