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Trial registered on ANZCTR

Registration number

ACTRN12624001010583

Ethics application status

Approved

Date submitted

22/05/2024

Date registered

20/08/2024

Date last updated

20/08/2024

Date data sharing statement initially provided

20/08/2024

Type of registration

Retrospectively registered

Titles & IDs

Public title

Does levodopa/carbidopa, a common Parkinson's Disease drug, affect stomach emptying, blood pressure and heart rate?

Scientific title

Acute effects of dopaminergic therapy with levodopa/carbidopa on the gastric emptying, blood pressure and superior mesenteric artery blood flow responses to oral glucose in patients with mild to moderate Parkinson’s disease.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Parkinson's disease

Postprandial hypotension

Delayed gastric emptying

Condition category

Condition code

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Metabolic and Endocrine

Other metabolic disorders

Neurological

Parkinson's disease

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Patients will attend on two separate occasions (after fasting from solids for 14 h and liquids for 12 h) at least five days apart.

At t= -60 minutes, the patient will then be given either
(1) an oral dose of levodopa (200mg)/carbidopa (50mg) (tablet) or
(2) matching placebo.

At t = -3 min, the patient will consume a drink comprising 75 g glucose labelled with 20 MBq 99mTc-calcium phytate, made up to 300ml water. The end of drink consumption will be recorded as t = 0 min

Patients will then undergo concurrent measurements of gastrointestinal (GI) symptoms (questionnaire), gastric emptying (scintigraphy) , blood pressure, heart rate (Dinamap) and superior mesenteric artery blood flow (Doppler ultrasound), blood glucose , serum insulin , and plasma levodopa (L-DOPA) concentrations for a period of 3 hours i.e. t= 0-180 min, following the drink.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

The effect of levodopa/carbidopa on the gastric emptying, blood pressure and superior mesenteric artery blood flow responses to oral glucose in patients will be compared to matched placebo (control- containing sucralose)

Control group

Placebo

Outcomes

Primary outcome [1]

Gastric emptying using Scintigraphy

Timepoint [1]

Gastric emptying will be measured continuously during the study (t=0-180 min) ie 1 min frames for the first 60 min and 3 min frames thereafter until t=180 min.

Secondary outcome [1]

Blood pressure using automated BP cuff (DINAMAP ProCare 100, GE Medical Systems, Milwaukee, WI, USA).

Timepoint [1]

Blood pressure will be measured at 3 min intervals for 9 min prior to administration of study drug, continuously prior to the ingestion of the drink (t = -60, -45, -30, -15, -3 minutes), and then regularly at 3-min intervals from t = 0 - 180 min.

Secondary outcome [2]

Heart rate using automated BP cuff (DINAMAP ProCare 100, GE Medical Systems, Milwaukee, WI, USA).

Timepoint [2]

Secondary outcome [3]

SMA blood flow using a Logiq GE doppler ultrasonography system (GE Healthcare Technologies, Sydney, NSW, Australia).

Timepoint [3]

SMA blood flow will be measured immediately before the study medication (t = -60 minutes) and before the drink consumption (t= -30 and -3 minutes) and then at t = 15, 30, 45, 60, 90, 120, 150 and 180 minutes.

Secondary outcome [4]

Sensation of dizziness using a visual analogue scale.

Timepoint [4]

Prior to the ingestion of the drink (t = -60, -30 and -3 minutes) and then at t = 15, 30, 45, 60, 90, 120 and 180 minutes.

Secondary outcome [5]

Blood glucose using a portable blood glucose meter (MediSense Companion 2 meter; MediSense Inc., Waltham, MA)

Timepoint [5]

Blood glucose will be measured prior to the ingestion of the drink (t = -60, -45, -30, -15 and -3 minutes) and then at t = 15, 30, 45, 60, 90, 120, 150, 180.

Secondary outcome [6]

Insulin using serum samples

Timepoint [6]

Serum insulin will be measured prior to the ingestion of the drink (t = -60, -45, -30, -15 and -3 minutes) and then at t = 15, 30, 45, 60, 90, 120, 150, 180.

Secondary outcome [7]

Levodopa level using plasma samples

Timepoint [7]

Levodopa level will be measured prior to the ingestion of the drink (t = -60, -45, -30, -15 and -3 minutes) and then at t = 15, 30, 45, 60, 90, 120, 150, 180.

Secondary outcome [8]

Sensation of hunger with visual analogue questionnaire

Timepoint [8]

Prior to the ingestion of the drink (t = -60, -30 and -3 minutes) and then at t = 15, 30, 45, 60, 90, 120 and 180 minutes.

Secondary outcome [9]

Sensation of fullness with visual analogue questionnaire

Timepoint [9]

Prior to the ingestion of the drink (t = -60, -30 and -3 minutes) and then at t = 15, 30, 45, 60, 90, 120 and 180 minutes.

Secondary outcome [10]

Sensation of desire to eat with visual analogue questionnaire

Timepoint [10]

Prior to the ingestion of the drink (t = -60, -30 and -3 minutes) and then at t = 15, 30, 45, 60, 90, 120 and 180 minutes.

Eligibility

Key inclusion criteria

• Patients currently taking short-acting levodopa/carbidopa
• Body Mass Index (BMI) 19 - 30 kg/m²
• A diagnosis of idiopathic PD according to the UK brain bank criteria of mild to moderate PD (Hoehn and Yahr Staging <2.5)

Minimum age

50 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

• History of diabetes mellitus (or fasting plasma glucose >7.0 mmol/L or HbA1C > or =6.5%), severe respiratory, cardiovascular, haematologic, hepatic and/or renal disease (creatinine clearance <50 mL/min), chronic alcohol abuse or epilepsy or if iron stores, or liver function tests are two times greater than the upper limit of the following normal ranges:

Alanine aminotransferase (ALT) < 55 U/L
Alkaline phosphatase (ALP) 30 - 110 U/L
Aspartate transaminase (AST) < 45 U/L
Total bilirubin 2 - 24 µmol/L
Haemoglobin 115 – 165 g/L (Females)
130 – 180 g/L (Males)
Ferritin 15 – 200 µg/L (Females)
30 – 300 µg/L (Males)

• Medication that influence BP or GI function
• Patients taking long-acting levodopa preparations
• History of GI disease (unrelated to PD), including known gastroparesis, significant upper GI symptoms and gastric surgery
• Smoking >10 cigarettes/day
• Alcohol consumption > 20 g/day
• Blood donation in the previous 12 weeks
• Pregnancy or breastfeeding
• Inability to withdraw from the morning dose of anti-Parkinsonian medication to allow a washout.
• Contraindications to levodopa/carbidopa, including current treatment with MAO inhibitor, known hypersensitivity, narrow-angle glaucoma, melanoma and suspicious undiagnosed skin lesions.

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)

Randomisation will be carried out by the Pharmacy at the Royal Adelaide Hospital. Allocation will involve contacting the holder of the allocation schedule (RAH Pharmacy) who is at a separate site to provide the medication (so that this is blinded to both the participant and study investigator).

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Sequence generation will be carried out by the Pharmacy at the Royal Adelaide Hospital using simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).

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

Intervention assignment

Crossover

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Data will be analysed using standardised, non-parametric statistical methods (e.g. using repeated measures ANOVA). Relationships between variables will be assessed by linear regression analysis.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

20/09/2018

Date of last participant enrolment

Anticipated

30/11/2025

Actual

Date of last data collection

Anticipated

31/12/2025

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Royal Adelaide Hospital Clinical Project Grant

Address [1]

Port Road, Adelaide SA 5000

Country [1]

Australia

Primary sponsor type

Individual

Name

Professor Karen Jones, The University of Adelaide

Address

NHMRC Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Level 5 Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA 5005

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Central Adelaide Local Health Network HREC

Ethics committee address [1]

https://www.rah.sa.gov.au/research/for-researchers/central-adelaide-local-health-network-human-research-ethics-committee

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

30/11/2016

Approval date [1]

13/06/2017

Ethics approval number [1]

R20161203

Summary

Brief summary

In this study, we are interested in looking at the acute effects of the anti-Parkinson drug, levodopa/carbidopa (Sinemet®) on the rate of stomach emptying, blood pressure and abdominal blood flow after a sugary drink, and the relationship between the rate of stomach emptying and the rise in levodopa levels.

The primary hypotheses underlying the study are that (i) a therapeutic dose of levodopa (200mg) / carbidopa (50mg) will slow gastric emptying in patients with mild to moderate Parkinson’s disease and (ii) this slowing of gastric emptying will be associated with an attenuation in the fall in blood pressure, and the rise in superior mesenteric artery (SMA) blood flow, after oral glucose.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Karen Jones

Address

Country

Australia

Phone

+61 8 8313 7821

Fax

[email protected]

Contact person for public queries

Name

Karen Jones

Address

The University of Adelaide, Level 5 Adelaide Health and Medical Sciences Building Cnr North Tce and George St Adelaide SA 5005 Australia

Country

Australia

Phone

+61 8 8313 7821

Fax

[email protected]

Contact person for scientific queries

Name

Karen Jones

Address

The University of Adelaide, Level 5 Adelaide Health and Medical Sciences Building Cnr North Tce and George St Adelaide SA 5005 Australia

Country

Australia

Phone

+61 8 8313 7821

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Data are to remain confidential to maintain participant anonymity

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.

Trial Review

Documents added manually

Documents added automatically