Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000191594p
Ethics application status
Submitted, not yet approved
Date submitted
15/01/2024
Date registered
27/02/2024
Date last updated
27/02/2024
Date data sharing statement initially provided
27/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating tolvaptan stimulated copeptin measurements for the differential diagnosis of polyuria-polydipsia syndrome
Scientific title
Investigating tolvaptan stimulated copeptin measurements for the differential diagnosis of polyuria-polydipsia syndrome
Secondary ID [1] 311328 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polyuria polydipsia syndrome 332581 0
Arginine vasopressin deficiency 332582 0
Primary polydipsia 332583 0
Condition category
Condition code
Metabolic and Endocrine 329279 329279 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will look at the response of the pituitary gland to a single dose of tolvaptan 30 mg oral capsule compared with placebo oral capsule. Administration will be supervised.
This is a crossover study where participants will attend for two study visits and receive the active treatment (tolvaptan 30 mg) on one study visit day and placebo on the other study visit day. The wash-out period between treatments is a minimum of 3 days.
Intervention code [1] 327771 0
Diagnosis / Prognosis
Intervention code [2] 327943 0
Treatment: Drugs
Comparator / control treatment
The comparator is a placebo capsule with an inert filler.
Three groups will be recruited: healthy volunteers, people with primary polydipsia, and people with arginine vasopressin deficiency.
Copeptin measurements following administration of tolvaptan will be compared between these groups.
Control group
Placebo

Outcomes
Primary outcome [1] 337098 0
Copeptin
Timepoint [1] 337098 0
Baseline and at 2, 4, 6 and 8 hours post tolvaptan or placebo
Secondary outcome [1] 430686 0
Plasma sodium
Timepoint [1] 430686 0
Baseline, 2, 4, 6 and 8 hours post tolvaptan or placebo
Secondary outcome [2] 430687 0
Urine output
Timepoint [2] 430687 0
Baseline, 2, 4, 6 and 8 hours post tolvaptan or placebo
Secondary outcome [3] 430688 0
Side effects including but not limited to thirst, urinary frequency, dry mouth, headache, nausea and vomiting, dizziness
Timepoint [3] 430688 0
Baseline, 1, 2, 3, 4, 5, 6, 7, and 8 hours post tolvaptan or placebo
Secondary outcome [4] 430693 0
Urine osmolality
Timepoint [4] 430693 0
Baseline, 2 hours and at completion of the study visit post tolvaptan or placebo

Eligibility
Key inclusion criteria
Healthy participants
o Age >18 years
o Healthy participant with no significant comorbidities

Participants with arginine vasopressin deficiency or primary polydipsia
- 18 years or older
- BMI 18.5 to 30 kg/m2
- polyuria >3L/day or >50mL/kg body weight/day or regular desmopressin administration.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Healthy volunteers
o BMI <18.5 kg/m2 or >30 kg/m2
o Vigorous physical exercise within 24 hours of study participation
o Alcohol intake or cigarette smoking within 24 hours of study participation
o Pregnancy and breastfeeding
o Evidence of disordered drinking habits (polyuria >50 mL/kg body weight and polydipsia >3L/24 hours)
o Acute illness
o Electrolyte abnormalities including hyponatraemia or other electrolyte disorders
o Significant medical comorbidities (cardiac, hepatic and kidney failure, diabetes mellitus, pituitary or adrenal disorders, untreated hypothyroidism, uncontrolled hypertension and epilepsy)
o Concomitant medications with the potential to interfere with the results (including those known to cause electrolyte disturbances and/or solute diuresis such as diuretics, glucocorticoids, anti-epileptic, anti-depressant and anti-emetic medications).

Participants with arginine vasopressin deficiency or primary polydipsia
o Vigorous exercise <24 hours before study participation
o Alcohol intake or cigarette smoking <24 hours before the study participation, pregnancy or breastfeeding
o Aacute illness.
o Significant medical comorbidities (cardiac, hepatic and kidney failure, diabetes mellitus, pituitary or adrenal disorders, untreated hypothyroidism, uncontrolled hypertension and epilepsy)
o Concomitant medications with the potential to interfere with the results (including those known to cause electrolyte disturbances and/or solute diuresis such as diuretics, glucocorticoids, anti-epileptic, anti-depressant and anti-emetic medications).

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be randomised at 1:1 ratio to receive either tolvaptan or placebo on the first study visit, and the alternative on the second study visit. 40 sealed envelopes will be pre-prepared, one for each participant, containing documentation outlining the sequence of study visit treatment (20 instructing tolvaptan on the first visit and placebo on the second visit and 20 instructing placebo on the first visit and tolvaptan on the second visit), and shuffled and randomly drawn for each participant. The envelopes will be prepared by the Principal Investigator (EB) and will be kept in a secured cabinet in the Diabetes and Endocrinology office. An envelope will only be opened after the participant’s name is written on the appropriate envelope to reveal the allocation sequence. A study nurse not involved in further study procedures will open the envelopes and be aware of the allocation and organise the study medications. The treatment sequence will be documented by another investigator and available to the primary investigator after completion of the study visits.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2024
Actual
Date of last participant enrolment
Anticipated
30/04/2025
Actual
Date of last data collection
Anticipated
30/05/2025
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 26023 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 41869 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 315581 0
Hospital
Name [1] 315581 0
Metro South Research Scheme, Princess Alexandra Hospital
Country [1] 315581 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital, Metro South Health Service
Address
Princess Alexandra Hospital
Country
Australia
Secondary sponsor category [1] 317676 0
None
Name [1] 317676 0
Address [1] 317676 0
Country [1] 317676 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314477 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 314477 0
Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland
Ethics committee country [1] 314477 0
Australia
Date submitted for ethics approval [1] 314477 0
14/02/2024
Approval date [1] 314477 0
Ethics approval number [1] 314477 0

Summary
Brief summary
The determination of a specific diagnosis in patients with polyuria syndromes is a frequent problem in clinical practice. Determining the correct diagnosis is crucial to optimising the management of these conditions as treatment approaches differ, and both inadequate and incorrect treatment can cause severe complications. However, differentiating these conditions, particularly arginine vasopressin deficiency (AVP-D) and primary polydipsia has proven very difficult and complex stimulation testing is needed for the diagnosis of AVP-D and primary polydipsia. This study will look at the response of the body's pituitary gland to a single dose of a medication called tolvaptan compared to placebo to see if this could be used as a new and simpler test for the diagnosis of these conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131722 0
Dr Emily Brooks
Address 131722 0
Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland, 4102
Country 131722 0
Australia
Phone 131722 0
+61 0731769562
Fax 131722 0
Email 131722 0
emily.brooks@health.qld.gov.au
Contact person for public queries
Name 131723 0
Dr Emily Brooks
Address 131723 0
Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland, 4102
Country 131723 0
Australia
Phone 131723 0
+61 0731769562
Fax 131723 0
Email 131723 0
emily.brooks@health.qld.gov.au
Contact person for scientific queries
Name 131724 0
Dr Emily Brooks
Address 131724 0
Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland, 4102
Country 131724 0
Australia
Phone 131724 0
+61 0731769562
Fax 131724 0
Email 131724 0
emily.brooks@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.