Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626000188336
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
27/01/2026
Date registered
Help: Date registered
13/02/2026
Date last updated
Help: Date last updated
31/08/2026
Date data sharing statement initially provided
Help: Data sharing statement date
13/02/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
Capillary and Inflammation Modulation for Migraine (CALM): A Double-Blind Evaluation of vascular-active, anti-inflammatory nutraceutical and semi-essential amino acid for migraine prevention in Australian adults.
Scientific title
Capillary and Inflammation Modulation for Migraine (CALM): A Double-Blind Evaluation of vascular-active, anti-inflammatory nutraceutical and semi-essential amino acid for migraine prevention in Australian adults.
Additional trial identifiers [1] 316365 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CALM (Capillary and Inflammation Modulation for Migraine)
Related trial records
This trial builds upon prior pilot work investigating L-arginine and garlic-derived nutraceutical interventions in migraine populations (ACTRN12621001476820 (LARGE Trial)).

Health condition
Health condition(s) studied:
Chronic frequent episodic migraine 340438 0
Condition category
Condition code
Neurological 336651 336651 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
A phase-II, randomised, double-blind, two-arm, 16-week study will be conducted in individuals with migraines. This study aims to evaluate the effects of a semi-essential amino acid alone or in combination with a vascular-active, anti-inflammatory nutraceutical on migraine associated pain and quality of life. Each participant will be randomised into the 2 arms and self-administer the allocated nutraceuticals.

Arm 1: Semi-essential amino acid + placebo
Arm 2: Semi-essential amino acid + Vascular-active, anti-inflammatory nutraceutical

The intervention will be provided as follows:
- Weeks 0–8: All receive a semi-essential amino acid.
- Weeks 9-16: Continue a semi-essential amino acid + randomised to either a vascular-active, anti-inflammatory nutraceutical or placebo daily.

Capsule counts will be conducted at study visits to ensure adequate adherence to intervention protocol.
Intervention code [1] 333028 0
Treatment: Other
Description of the comparator or control
Placebo (daily 0.2g cellulose in oral gelatin capsules)
Control group
Placebo

Outcomes
Primary outcome [1] 344167 0
Migraine-related quality of life
Timepoint [1] 344167 0
Baseline, every 4 weeks over the 16-week study, end of study (primary endpoint)
Primary outcome [2] 344168 0
Migraine pain type with frequency
Timepoint [2] 344168 0
Baseline, every 2 weeks over the 16-week study, end of study (primary endpoint)
Primary outcome [3] 344254 0
Migraine severity
Timepoint [3] 344254 0
Baseline, every 2 weeks over the 16-week study, end of study (primary endpoint)
Secondary outcome [1] 456912 0
Unexpected effects of our treatment
Timepoint [1] 456912 0
Every 4 weeks over the 16-week study, end of study
Secondary outcome [2] 456913 0
Concentration of blood asymmetric dimethyl-arginine taken from antecubital fossa
Timepoint [2] 456913 0
Baseline, every 8 weeks over the 16-week study, end of study
Secondary outcome [3] 457244 0
Concentration of blood nitrite taken from antecubital fossa
Timepoint [3] 457244 0
Baseline, every 8 weeks over the 16-week study, end of study
Secondary outcome [4] 457245 0
Concentration of blood endothelin 1 taken from antecubital fossa
Timepoint [4] 457245 0
Baseline, every 8 weeks over the 16-week study, end of study

Eligibility
Key inclusion criteria
1. Migraine (with or without aura) diagnosis at least 12 months ago
2. Migraine onset occurred before 50 years of age
3. Males and females, aged at least 18 years at screening
4. Participants must report experiencing =4 migraine days per
month over the previous 3 months
5. Able to differentiate between migraine and “other” headache types
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
1. Any change in medications that affect blood vessel width or blood pressure during the study
2. Diagnosis of headache disorder, facial pain disorder or other neurological disorder other than migraine
3. Change in migraine treatment in previous 3 months
4. Taking L-arginine tablets or garlic extracts in previous 3 months
5. Known allergies to foods containing L-arginine or garlic
6. Known risks of bleeding or coagulopathy, or currently on blood-thinning medications
7. Active cancer diagnosis with exception to cancers of the skin such as basal or squamous cell carcinoma in situ of the skin
8. Presence of acute/chronic pain disorders, infections, cardiovascular or cerebrovascular disease
9. Diagnoses other than migraine as primary cause of headaches
11. Procedure or injection to treat migraine over past 3 months
12. Implanted or external nerve stimulator to treat migraines
13. History of diabetes, hypertension, hypotension, collagen vascular disease, vasculitis, or renal disease/failure
14. Smoke >1 pack of cigarettes a day
15. Clinically significant anaemia or iron deficiency
16. Participation in concurrent research study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All study capsules will be identical in appearance, packaging, and labelling. Each participant's treatment pack will be labelled with a unique participant identification code to maintain blinding.

An independent researcher/statistician will generate the randomisation schedule and assign participants to a treatment group. They will be the only person with access to the allocation list and will be responsible for labelling each participant's treatment pack in accordance with the randomisation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary analysis will follow an intention-to-treat (ITT) approach, with per-protocol (PP) sensitivity analyses. All statistical tests will be two-tailed, with a significance threshold of a = 0.05. Where relevant, 95% confidence intervals (CIs) and effect sizes will be reported. Analyses will be conducted using Stata (v16), R (v4.0 or later), or SPSS (v26 or later).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
23/04/2026
Actual
20/05/2026
Date of last participant enrolment
Anticipated
14/05/2027
Actual
Date of last data collection
Anticipated
14/09/2027
Actual
Sample size
Target
160
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 320974 0
Charities/Societies/Foundations
Name [1] 320974 0
MSWA
Country [1] 320974 0
Australia
Funding source category [2] 320987 0
Charities/Societies/Foundations
Name [2] 320987 0
Goshar Mepa Maroo Legacy Fund
Country [2] 320987 0
Australia
Primary sponsor type
University
Name
Curtin
Address
Country
Australia
Secondary sponsor category [1] 323669 0
Other Collaborative groups
Name [1] 323669 0
Perron Institute for Neurological and Translational Science
Address [1] 323669 0
Country [1] 323669 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 319507 0
Curtin University Human Research Ethics Committee
Ethics committee address [1] 319507 0
Ethics committee country [1] 319507 0
Australia
Date submitted for ethics approval [1] 319507 0
23/05/2025
Approval date [1] 319507 0
24/09/2025
Ethics approval number [1] 319507 0
HRE2025-0528

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 147550 0
Prof John Mamo
Address 147550 0
Curtin Medical Research Institute, Curtin University, Building 305, Kent Street, Bentley, Western Australia 6102
Country 147550 0
Australia
Phone 147550 0
+61 08 9266 7232
Fax 147550 0
Email 147550 0
[email protected]
Contact person for public queries
Name 147551 0
John Mamo
Address 147551 0
Curtin Medical Research Institute, GPO Box U1987, Perth WA 6845
Country 147551 0
Australia
Phone 147551 0
+61 08 9266 7232
Fax 147551 0
Email 147551 0
[email protected]
Contact person for scientific queries
Name 147552 0
John Mamo
Address 147552 0
Curtin Medical Research Institute, GPO Box U1987, Perth WA 6845
Country 147552 0
Australia
Phone 147552 0
+61 08 9266 7232
Fax 147552 0
Email 147552 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.