臨床研究等提出・公開システム

Date of registration	April. 10, 2020
Last modified on	Mar. 18, 2021
Trial ID	jRCT2080225159

Scientific Title	Effects of adrenomedullin in steroid-resistant patients with ulcerative colitis: randomized, double-blind, placebo-controlled phase 2a clinical trial
Public Title	Phase 2a clinical trial for ulcerative colitis using adrenomedullin

Completion Date or Terminated date	April. 25, 2019
Actual Enrolled Number	28
Baseline Characteristics	Patients with steroid-resistant ulcerative colitis
Participant flow	We obtained informed consent from 30 patients, and then two patients were excluded due to unfitness to the criteria. The remaining 28 patients were enrolled in this study, and 26 patients received the drug, but five patients dropped out within 14 days, and thus 21 patients completed the 14 days administration. Of the 21 patients, only 12 patients completed the 8 weeks follow-up.
Adverse events	Only one patient in the 10 ng/kg/min group terminated the administration because of headaches and a decrease in blood pressure, which were caused due to the vasodilatory effect of AM. However, these AEs were observed to quickly disappear after termination of drug administration. The reported AEs are summarized in Table 4. Symptoms related to the vasodilatory effect of AM, such as headaches, palpitations, decreases in blood pressure, and flushes, were more frequently observed in the AM-treated groups than the placebo group. However, these symptoms were mild and tolerable without any treatments, except for the one patient mentioned above. An SAE reported to have occurred in one patient in the placebo group was that of infectious pneumonia (Pneumococcus and Pneumocystis) and related adrenal insufficiency 1 month after the end of the placebo administration. This patient recovered after appropriate treatment, and this SAE was judged by the investigators to not be related to the study drug.
Primary Outcome Measures	We did not observe any differences among the four groups for the primary endpoint, the changes in Mayo scores at 2 weeks.
Secondary Outcome Measures	The Mayo score at 8 weeks was shown to be significantly decreased only in the group of patients receiving high-dose AM (15 ng/kg/min) compared with the placebo group.
Brief summary	Despite the limited number of patients in this double-blind randomized trial, we observed the successful complete remission at 8 weeks in patients with steroid-resistant UC receiving a high dose of AM. Hence, AM could serve as candidate potent therapeutic agent for complete remission in refractory UC.
Posting of journal publication
Date of the first journal publication of results	Nov. 02, 2020
URL hyperlink(s) related to results and publications	https://link.springer.com/article/10.1007/s00535-020-01741-4

Plan to share IPD	No
Plan description
URL link to protocol file(s)
Version of protocol file(s)	version: date:

Contact for Scientific Queries	Name
	Contact Name for Scientific Queries	Faculty of Medicine, University of Miyazaki
	Address	5200 Kihara, Miyazaki, Miyazaki 889-1692, Japan
	Phone Number	+81-985-85-0872
	E-mail Address	toshihiro_kita@med.miyazaki-u.ac.jp

Contact for Public Queries	Name
	Contact Name for Public Queries	Faculty of Medicine, University of Miyazaki
	Address	5200 Kihara, Miyazaki, Miyazaki 889-1692, Japan
	Phone Number	+81-985-85-0872
	E-mail Address	toshihiro_kita@med.miyazaki-u.ac.jp

Recruitment Status	completed

Date of First Enrolment		Mar. 29, 2017
Target Sample Size		32
Study Type		Interventional
Study Design	Study Design	multicenter, randomized, double-blind, placebo-controlled study
Study Design	Objective	treatment purpose
Phase		2
Key inclusion & exclusion criteria	Inclusion Criteria	patients with steroid-resistant ulcerative colitis
	Exclusion Criteria	Patient using biologics Patient with fulminant ulcerative colitis (UC) Patient need early operation for UC Patient with precancerous lesion(s) in the colon Patient with active infection Patient with severe complication(s) Patient with malignancy or past history of malignancy Pregnant woman
	Minimum Age	18age old over
	Maximum Age	75age old under
	Gender	Both
Health Condition or Problem Studied		ulcerative colitis
Intervention(s)		investigational material(s) Generic name etc : adrenomedullin INN of investigational material : adrenomedullin Therapeutic category code : 249 Other hormone preparations (including antihormone preparations) Dosage and Administration for Investigational material : Continuous intravenous infusion for 8 hours per day control material(s) Generic name etc : placebo INN of investigational material : placebo Therapeutic category code : --- Other Dosage and Administration for Investigational material : Continuous intravenous infusion for 8 hours per day
Health Condition(s) Keyword
Intervention(s) Keyword
Health Condition(s) Code
Intervention(s) Code
Primary Outcome		efficacy change of Mayo scores at week 2
Secondary Outcome		safety efficacy change of Mayo scores at week 8 effective rate of Mayo scores improvement of Mayo scores Lichtiger index Mayo endoscopy sub-score (MES) fecal immunochemical test and calprotectin at week 2 dose of steroid

Primary Sponsor	University of Miyazaki
Secondary Sponsor	-

Name of Funding Organization	Japan Agency for Medical Research and Development
Name of Research Funding	Practical Research Project for Rare/Intractable Diseases

Name of IRB	Institutional Review Board of University of Miyazaki
Address of IRB	5200 Kihara, Miyazaki, Miyazaki 889-1692, Japan
Phone Number of IRB	+81-985-85-9852
E-mail Address of IRB	chiken-jimu@med.miyazaki-u.ac.jp
Status of IRB Review	approved
Date of Approval by IRB	Nov. 22, 2016

Secondary ID No.	JapicCTI-205255
Name of Other Registries

Countries / Regions of Recruitment	Japan

History of Changes

No	Publication date
2	Mar. 18, 2021	(this page)	Changes
1	May. 01, 2020	Detail

List of change history