Skip to main content
OpenTrials
Completed

NCT Number: NCT04164849

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

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 up to 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 for the first 5 patients. The latter 5 patients will be referred to standard of care on the week 13 visit. 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).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Crohn Disease Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Akershus University Hospital

Lorenskog, Akershus, 1478, Norway

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Provision of informed consent
  • Age above 18
  • Male or female patient with active Crohn's disease (6)
  • Women of childbearing potential (WOCBP) will have to use highly effective methods of contraception throughout the entire study.
  • 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

  • Active inflammation in the gut documented by
  • Harvey Bradshaw Index >5 and
  • 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
  • Inflammatory marker; fecal calprotectin > 250 and/or C reactive protein > 5

Exclusion criteria

  • Photosensitive comorbidities, porphyria or known hypersensitivity to 5-aminolevulinic acid or porphyrins
  • Patients with aphakia
  • 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.
  • 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
  • Subjects with polyneuropathy
  • Uncontrolled infection or fever
  • History of heparin-induced thrombocytopenia, absolute neutrophil count <1x109, platelet count <20x10 9
  • Body weight below 40 kg
  • Investigator considers subject unlikely to comply with study procedures, restrictions and requirements.
  • Presence of other gastrointestinal diseases potentially influencing the study endpoints
  • 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.

Treatment and study plan

5-Aminolevulinic Acid

Drug

5-aminolevulinic acid (30 mg/ml) will be added to mononuclear cells in a dose of 3 millimolar and incubated for 1 hour

Blue light photopheresis

Procedure

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

Transfusion

Procedure

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

Continuous Mononuclear Cell Collection (CMNC)

Procedure

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 outcomes

  1. Clinical response

    Time frame: Week 13, 26 (28 for patients not eligible for study extension and the latter 5 patients), 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) 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 and latter 5 patients) in addition to week 64 and 3 months after last treatment.

    Changes in Serum Carbamide (millimol/L) before and after treatment

Secondary outcomes

  1. CD4+ and CD8+ T cell subpopulations

    Time frame: Week 0, 10 (all patients) and 50 (patients of the first 5 subjects eligible for study extension)

    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 (all patients) and 50 (patients of the first 5 subjects eligible for study extension)

    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 and the latter 5 patients), 38, 50, 64 and 3 months after last treatment.

    Harvey Bradshaw Index < 5 points

  4. Endoscopic efficacy

    Time frame: Week 13 (all patients) and 64 (patients of the first 5 subjects eligible for study extension) 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 and the latter 5 patients), 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 and the latter 5 patients), 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 and the latter 5 patients), 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 and the latter 5 patients), 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.

Sponsors and collaborators

Lead sponsor

University Hospital, Akershus

Other

Collaborators

  • Oslo University Hospital

Registry information

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Nov 15, 2019
Registry last updated
Jan 30, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.