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Trial registered on ANZCTR


Registration number
ACTRN12621000097842
Ethics application status
Approved
Date submitted
3/12/2020
Date registered
1/02/2021
Date last updated
14/03/2022
Date data sharing statement initially provided
1/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The New Zealand Indigo naturalis dose-escalation study (NZ-INDES): a study to investigate its effect on immune responses in healthy volunteers
Scientific title
Impact of a single intake of Indigo naturalis on the activity of blood aryl hydrocarbon receptor in healthy individuals
Secondary ID [1] 302940 0
None
Universal Trial Number (UTN)
U1111-1261-6580
Trial acronym
NZ-INDES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inflammation 320245 0
Condition category
Condition code
Inflammatory and Immune System 317902 317902 0 0
Normal development and function of the immune system
Alternative and Complementary Medicine 318178 318178 0 0
Herbal remedies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study design:
This is a single dose, open-label, dose-escalation pilot study. Following a lead-in period for screening, recruitment, participants will be allocated either to a zero-dose control group, or, only one of the four different (Dose 1 - 4 ) Indigo naturalis dose groups stated below. The study involves a single 24 h intervention period over two study visits.

Intervention items:
Control intervention item: zero-dose control (capsules containing 2 g of microcrystalline cellulose)
Dose 1: 0.25 g Indigo naturalis (capsules containing 0.25 g Indigo naturalis powder)
Dose 2: 0.5 g Indigo naturalis (capsules containing 0.5 g Indigo naturalis powder)
Dose 3: 1 g Indigo naturalis (capsules containing 1 g Indigo naturalis powder)
Dose 4: 2 g Indigo naturalis (capsules containing 2 g Indigo naturalis powder)

Mode of administration: Oral (capsule form)

Strategy used to monitor adherence: Capsules containing either 2 g microcrystalline cellulose (zero-dose control) or a particular dose (0.25 g, 0.5 g, 1 g, or 2 g) of Indigo naturalis, will be administered to a particular participant under the direct supervision of a clinical research nurse. Hence, adherence to the intervention is directly monitored, confirmed and recorded on site.

Method of allocation:
This study is a non-randomised study where participants will be allocated to either the zero-dose control (2 g of microcrystalline cellulose), or a specific dose of Indigo naturalis (0.25 g, 0.5 g, 1 g, or 2 g), in the order in which they are enrolled into the study. Once five participants have been recruited to receive a particular intervention, the next five participants will be allocated to the next subsequent dose of Indigo naturalis.
Intervention code [1] 319227 0
Treatment: Other
Comparator / control treatment
Capsules containing 2 g microcrystalline cellulose
Control group
Placebo

Outcomes
Primary outcome [1] 325918 0
Changes in blood Aryl hydrocarbon receptor (AhR) activity, as determined by measuring the level of AhR activity in plasma sampled across five time points (0 h [baseline, fasted], 1, 3, 6 and 24 h) over the course of the 24 h intervention, using a stable human cell-based AhR luciferase reporter assay.
Timepoint [1] 325918 0
(0 h [baseline, fasted], 1, 3, 6 and 24 h) over the course of the 24 h intervention
Secondary outcome [1] 389502 0
Changes in the expression level of the prototypical downstream AhR-regulated protein target, CYP1A1 in peripheral blood mononuclear cells, isolated from whole blood, by flow cytometry.
Timepoint [1] 389502 0
(0 h [baseline, fasted], 1, 3, 6 and 24 h) over the course of the 24 h intervention
Secondary outcome [2] 389503 0
Changes in plasma levels of the AhR-regulated cytokine, interleukins 22 (IL-22), as determined by cytokine ELISA.
Timepoint [2] 389503 0
(0 h [baseline, fasted], 1, 3, 6 and 24 h) over the course of the 24 h intervention
Secondary outcome [3] 389504 0
Changes in liver function determined as a composite of alanine aminotransferase, alkaline phosphatase, bilirubin, assessed in serum sampled at various time points (1, 3, 6 and 24 h) and compared to the those found at baseline (0 h).
Timepoint [3] 389504 0
(0 h [baseline, fasted], 1, 3, 6 and 24 h) over the course of the 24 h intervention
Secondary outcome [4] 390311 0
Changes in plasma levels of the AhR-regulated cytokine, interleukin 10 (IL-10), as determined by cytokine ELISA.
Timepoint [4] 390311 0
[0 h [baseline, fasted], 1, 3, 6 and 24 h) over the course of the 24 h intervention

Eligibility
Key inclusion criteria
a. Anybody residing in Wellington (New Zealand), self-reported as healthy
b. Age between 18 to 65 years old
c. Participants must be willing to not consume any alcohol; use tobacco, e-cigarettes, or recreational drugs for at least 3 days prior to the study, and during the study visit days.
d. Not take any dietary supplement (e.g. vitamins, fortified drinks) and herbal medicines for at least 3 days prior to the study, and during the study visit days.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
a. Any known recent or current communicable diseases (e.g. HIV, hepatitis, etc.)
b. BMI < 18 kg/m2 or BMI > 35 kg/m2
c. Autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), celiac disease, pancreatitis or other malabsorption condition.
d. Chronic obstructive pulmonary disease (COPD) or other chronic respiratory conditions (including sleep apnoea)
e. Cardiovascular disease (CVD) current angina; myocardial infarction or stroke within the past 6 months; heart failure; symptomatic peripheral vascular disease; SBP > 160 mmHg and/or DBP > 100 mmHg (with or without hypertensive medication)
f. Type 1 or type 2 diabetes mellitus
g. Chronic renal impairment; liver disease e.g. cirrhosis; prior bariatric surgery, neurological, psychiatric, or musculoskeletal disease (e.g. rheumatoid arthritis); history of abnormal liver function
h. History of malignancy within the last 5 years, with the exception of basal cell carcinoma that has been completely excised prior to study entry remain eligible;
i. Recent prior (previous 4 weeks) or current use of antibiotics
j. Recent prior (previous 4 weeks) or current respiratory infection
k. Current or prior eating disorder (e.g. anorexia nervosa, bulimia)
l. Food allergy or intolerance, including gluten, soy, dairy, nuts & seed intolerance
m. Pregnant or breastfeeding; or intent to become pregnant during study duration
n. Current participation in another clinical intervention study
o. Inability to provide written informed consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/03/2021
Actual
26/02/2021
Date of last participant enrolment
Anticipated
1/12/2021
Actual
1/11/2021
Date of last data collection
Anticipated
31/12/2021
Actual
26/11/2021
Sample size
Target
25
Accrual to date
Final
25
Recruitment outside Australia
Country [1] 23268 0
New Zealand
State/province [1] 23268 0
Wellington

Funding & Sponsors
Funding source category [1] 307363 0
Government body
Name [1] 307363 0
The New Zealand High Value Nutrition (itself funded by the New Zealand Ministry of Business, Innovation and Employment)
Country [1] 307363 0
New Zealand
Primary sponsor type
Other
Name
Malaghan Institute of Medical Research
Address
Malaghan Institute of Medical Research
Gate 7, Victoria University, Kelburn Parade
Wellington 6242
New Zealand
Country
New Zealand
Secondary sponsor category [1] 308003 0
Government body
Name [1] 308003 0
Capital & Coast District Health Board (CCDHB)
Address [1] 308003 0
Clinical Trials Unit
CCDHB
Wellington Regional Hospital, Riddiford Street, Newtown, Wellington 6021
New Zealand
Country [1] 308003 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307448 0
Southern Health and Disability Ethics Committees
Ethics committee address [1] 307448 0
Ministry of Health
Ethics Department Reception - Ground Floor 20 Aitken Street Thorndon
WELLINGTON, 6011
Ethics committee country [1] 307448 0
New Zealand
Date submitted for ethics approval [1] 307448 0
23/11/2020
Approval date [1] 307448 0
18/12/2020
Ethics approval number [1] 307448 0

Summary
Brief summary
This is a single dose open-label dose-escalation pilot study. Following a lead-in period for screening, recruitment, participants will be allocated to a zero-dose control group or different Indigo naturalis dose groups. The study involves a single 24 h intervention period over two study visits.
Participants will be self-reported healthy adults (male or female, 18 – 65 years old), which represent the adult general population residing in Wellington, New Zealand. Following informed consent, the first five participants will take capsules containing 2 g of microcrystalline cellulose (zero-dose control group). The next group of five participants will take the lowest dose of Indigo naturalis. If data analysis of the lowest dose shows no detrimental effect on liver function, the next group of 5 individuals will take the next dose (0.5 g) of the herbal medicine and so on.
If we find a consistent, significant change in blood AhR activity in plasma and/or PBMCs in this pilot study, we intent to subsequently conduct a follow up study involving administering Indigo naturalis in people with inflammatory conditions, such those associated with obesity, metabolic syndrome, diabetes or liver steatosis.
Trial website
Trial related presentations / publications
Public notes
To contact Dr. Olivier Gasser, please dial +6444996914 and input '806' for the extension number

To contact Dr. Jeffry Tang, please dial +6444996914 and input '852' for the extension number

Contacts
Principal investigator
Name 107274 0
Dr Olivier Gasser
Address 107274 0
Malaghan Institute of Medical Research
Gate 7, Victoria University
Kelburn Parade
Wellington 6012
New Zealand
Country 107274 0
New Zealand
Phone 107274 0
+6444996914
Fax 107274 0
Email 107274 0
[email protected]
Contact person for public queries
Name 107275 0
Olivier Gasser
Address 107275 0
Malaghan Institute of Medical Research
Gate 7, Victoria University
Kelburn Parade
Wellington 6012
New Zealand
Country 107275 0
New Zealand
Phone 107275 0
+6444996914
Fax 107275 0
Email 107275 0
[email protected]
Contact person for scientific queries
Name 107276 0
Jeffry Tang
Address 107276 0
Malaghan Institute of Medical Research
Gate 7, Victoria University
Kelburn Parade
Wellington 6012
New Zealand
Country 107276 0
New Zealand
Phone 107276 0
+6444996914
Fax 107276 0
Email 107276 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification, will be made available upon publication.
We intend to publish all results. However, these results may be segmented into several publications.
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Anyone who wishes to access the data.
Available for what types of analyses?
Any analyses
How or where can data be obtained?
Data will be available through the publisher of the research articles.

De-identified, raw, line-by-line individual participant data may be made available by emailing the principal investigator (Dr. Olivier Gasser) at [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.