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Safety of indigo naturalis in patients with autoimmune pancreatitis (Indigo naturalis for autoimmune pancreatitis)

The treatment using indigo naturalis for autoimmune pancreatitis (Indigo naturalis for autoimmune pancreatitis)

5

Seven patients with autoimmune pancreatitis (AIP) were enrolled in this study. After enrollment, two patients were excluded due to not meeting the treatment initiation criteria, and five patients completed 8 weeks of treatment with Indigo naturalis (IN) 1.0 g/day. Key background characteristics: Age: Median 68 years (range 55-78) Sex: 3 males, 2 females Diagnosis: All patients met the International Consensus Diagnostic Criteria (ICDC) for definite AIP Prior treatment: Steroid-naive: 4 patients History of relapse: 1 patient (steroid-resistant case) Comorbidities: None of significance Follow-up duration: Median 549 days (range 87-1047)

This was a single-center, prospective, open-label, non-controlled clinical study (jRCTs051210171). Enrollment and participant flow: Planned enrollment: 7 patients Actual enrollment: 7 patients Excluded after enrollment: 2 patients Neuroleptic malignant syndrome: 1 Liver dysfunction: 1 Final analysis set: 5 patients (all completed the full 8-week intervention) No dropouts occurred, and all five participants completed both the treatment and follow-up periods.

(1) Serious Adverse Events (SAEs) No serious adverse events were observed during the 8-week IN treatment period or throughout follow-up. (2) Adverse Event of Special Interest: Pulmonary Arterial Hypertension (PAH) PAH has been reported in cases receiving high-dose IN (>2 g/day) and long-term treatment (>13 months). In this study (1.0 g/day for 8 weeks): Chest radiography Electrocardiography Echocardiography showed no abnormalities, and no findings suggestive of PAH were detected. (3) Other Adverse Events No gastrointestinal symptoms, liver dysfunction, or other adverse events requiring treatment discontinuation occurred. (4) Recurrence of AIP One patient experienced recurrence 5 months after completing IN therapy and was treated with corticosteroids. This patient had a pre-existing history of steroid resistance.

Primary Endpoint: Safety Administration of IN 1.0 g/day for 8 weeks resulted in no serious adverse effects. No incidence of PAH or other known severe risks was observed. Thus, the treatment regimen was evaluated as safe. Secondary Endpoints: Efficacy (1) Symptoms (Abdominal Pain NRS) All patients showed significant improvement in NRS by week 2. At week 8, NRS = 0 in all patients (complete resolution). Symptom improvement was maintained beyond week 24. (2) Imaging Findings (CT and FDG-PET) CT scans showed no marked reduction in pancreatic enlargement, indicating a response pattern distinct from steroid therapy. Among three patients evaluated by FDG-PET, two demonstrated reduced FDG uptake as early as week 2, suggesting decreased inflammatory activity. (3) Immunological Markers (IgG Subclasses and Cytokines) Significant changes observed: Marker Change: IgG1 Decreased IgG2 / IgG3 Increased IFN-gamma Decreased IL-22 Increased Markers without significant change: Total IgG IgG4 IFN-alpha IL-33 Interpretation: IN components (indigo, indirubin) may activate aryl hydrocarbon receptor (AhR) in the gut, leading to: IL-22 elevation Suppression of IFN-gamma Downregulation of IgG1 class-switching This suggests a unique immunomodulatory mechanism, distinct from corticosteroids.

This study evaluated the safety and efficacy of Indigo naturalis 1.0 g/day for 8 weeks in five patients with AIP. No serious adverse events occurred, and the treatment demonstrated a favorable safety profile. Abdominal pain improved rapidly in all patients, and FDG-PET confirmed reduced inflammatory activity in a subset of cases. Immunologic analyses indicated that IN may exert selective immunoregulatory effects via IL-22, differing markedly from the mechanism of corticosteroids.

Jan. 23, 2026

No

non

https://jrct.mhlw.go.jp/latest-detail/jRCTs051210171

Kamata Ken

Kindai University Hospital

377-2,Ohno-Higashi,Osaka-Sayama,Osaka,Japan

ky11@leto.eonet.ne.jp

Kamata Ken

Kindai University Hospital

377-2,Ohno-Higashi,Osaka-Sayama,Osaka,Japan

+81-72-366-0221

ky11@leto.eonet.ne.jp

Complete

Feb. 07, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Confirmed cases of naived autoimmune pancreatitis according to the clinical diagnosis criteria 2018 (For the patients previously treated with steroid more than 180 days or more should be passed since the latest administration.)
2. Patients with abdominal symptoms
3. Patients who are 20 years old or older at the time of consent
4. Patients who can provide written consent in person.

1. Patients with a history of adverse reactions or allergies to Chinese herbal medicines
2. Patients who have received other Chinese herbal medicines within 2 weeks prior to the registration date
3. Patients with a history of pulmonary arterial hypertension
4. Patients with obstructive jaundice
5. Patients with retroperitoneal fibrosis, interstitial pneumonia, or tubulointerstitial nephritis who present
clinically problematic symptoms and signs
6. Patients with pseudotumor of the liver or lung
7. Patients with serious infectious diseases
8. Patients with serum creatinine level of 2.0 mg/dl or higher
9. Patients with AST or ALT levels of 50 IU/l or higher
10. Patients who are pregnant, may become pregnant, are lactating, or wish to become pregnant during the study period
11. Patients who are judged inappropriate for inclusion in this study by the physician in charge

Both

Autoimmune pancreatitis

Administration of indigo naturalis

Autoimmune pancreatitis

indigo naturalis

084

Safety during the study

1. Rate of remission at 2 weeks
2. Rate of remission at 8 weeks
3. Rate of remission at 24 weeks
4. Evaluation of the AhR-IL-22 pathway

+81-744-29-8835

Jan. 26, 2022

none