Clinical Trial Results:
The influence of metformin and a hypocaloric diet on thyroid radioactive iodide uptake in healthy volunteers: a pilot study
Summary
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EudraCT number |
2016-001455-42 |
Trial protocol |
NL |
Global end of trial date |
02 Jun 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Feb 2020
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First version publication date |
11 Feb 2020
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Other versions |
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Summary report(s) |
Article Scientific Reports on Pilot study |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NL56309.091.16
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Nederlands Trial Register: NTR5853 | ||
Sponsors
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Sponsor organisation name |
Radboud Universitair Medisch Centrum
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Sponsor organisation address |
Geert Grooteplein Zuid 8, Nijmegen , Netherlands,
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Public contact |
Internal Medicine-Endocrine Disease, Radboud Universitair Medisch Centrum, 0031 0243614599,
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Scientific contact |
Internal Medicine-Endocrine Disease, Radboud Universitair Medisch Centrum, 0031 0243614599,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Aug 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Jun 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Jun 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the physiological effects of metformin and hypocaloric dieting on thyroid iodide uptake and thyroid function in healthy volunteers.
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Protection of trial subjects |
A complete health screening before enrollment was performed.
Participants were sent home with contact information and clear instructions when to contact the emergency number
During the intervention period, participants were contacted one week after starting intervention to check whether there are any complaints or complications or questions
Because of the low risk of either intervention, no additional specific measurements are taken.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 May 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 19
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Worldwide total number of subjects |
19
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EEA total number of subjects |
19
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
19
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were invited to participate through advertisements on the Radboud University Medical Centre website and local university websites and placement of advertisements in the medical faculty, other locations on campus and in the city centre between October and April 2017 | ||||||||||||||||
Pre-assignment
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Screening details |
Complete medical history and physical examination, including height, weight, BMI, and hip- and waist circumferences, and skinfold measurements.. A laboratory test was performed for screen for kidney disorder and thyroid disorders. | ||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
29 [1] | ||||||||||||||||
Number of subjects completed |
19 | ||||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Consent withdrawn by subject: 9 | ||||||||||||||||
Reason: Number of subjects |
Protocol deviation: 1 | ||||||||||||||||
Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: More possible participants were screened; 9 of them dropped out before start of the trial; therefore, according to the protocol, we recruited more participants and screened them to reach our desired number for each subgroup. |
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Period 1
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Period 1 title |
baseline
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Baseline - controle | ||||||||||||||||
Arm description |
- | ||||||||||||||||
Arm type |
No intervention | ||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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baseline diet | ||||||||||||||||
Arm description |
- | ||||||||||||||||
Arm type |
No intervention | ||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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baseline metformin | ||||||||||||||||
Arm description |
- | ||||||||||||||||
Arm type |
baseline | ||||||||||||||||
Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
PR1
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
during baseline: no metformin intake
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Period 2
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Period 2 title |
Intervention period
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Is this the baseline period? |
No | ||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Control | ||||||||||||||||
Arm description |
Iodide depleted diet | ||||||||||||||||
Arm type |
No intervention | ||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Hypocaloric diet | ||||||||||||||||
Arm description |
Hypocaloric diet; 40% caloric restriction (maximum of 1500 kcal/day) with high fat/low carbohydrate content (50% fat, 30% carbohydrate, 20% protein) for two weeks. | ||||||||||||||||
Arm type |
intervention | ||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Metformin | ||||||||||||||||
Arm description |
2-week course of metformin according to a dosing schedule | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
PR1
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dosing of Metformin:
• Day 1: 1 x 500 mg (dinner)
• Day 2: 1 x 500 mg (breakfast) & 1 x 500 mg (dinner)
• Day 3: 1 x 500 mg (breakfast) & 1 x 500 mg (dinner)
• Day 4: 1 x 500 mg (breakfast) & 2 x 500 mg (dinner)
• Day 5: 2 x 500 mg (breakfast) & 2 x 500 mg (dinner)
• Day 6 –End of study: 2 x 500 mg (breakfast) & 2 x 500 mg (dinner)
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Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
PR1
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dosing of Metformin:
• Day 1: 1 x 500 mg (dinner)
• Day 2: 1 x 500 mg (breakfast) & 1 x 500 mg (dinner)
• Day 3: 1 x 500 mg (breakfast) & 1 x 500 mg (dinner)
• Day 4: 1 x 500 mg (breakfast) & 2 x 500 mg (dinner)
• Day 5: 2 x 500 mg (breakfast) & 2 x 500 mg (dinner)
• Day 6 –End of study: 2 x 500 mg (breakfast) & 2 x 500 mg (dinner)
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Baseline characteristics reporting groups
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Reporting group title |
baseline
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Baseline - controle
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Reporting group description |
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Reporting group title |
baseline diet
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Reporting group description |
- | ||
Reporting group title |
baseline metformin
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Reporting group description |
- | ||
Reporting group title |
Control
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Reporting group description |
Iodide depleted diet | ||
Reporting group title |
Hypocaloric diet
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Reporting group description |
Hypocaloric diet; 40% caloric restriction (maximum of 1500 kcal/day) with high fat/low carbohydrate content (50% fat, 30% carbohydrate, 20% protein) for two weeks. | ||
Reporting group title |
Metformin
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Reporting group description |
2-week course of metformin according to a dosing schedule |
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End point title |
Thyroid iodide uptake [1] | ||||||||||||
End point description |
Primary endpoint of this study is to assess the effect of metformin and hypocaloric diet on thyroid iodide uptake. 123I thyroid uptake is measured by RAIU testing using a gamma probe. Uptake is presented as percentage of total administrated 123I after 4, 24 and 48 hours after ingestion I-123.
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End point type |
Primary
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End point timeframe |
thyroid uptake is measured by RAIU testing using a gamma probe. Uptake is presented as percentage of total administrated 123I after 4, 24 and 48 hours after ingestion I-123.
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: See summary document for full discription on statiscal analysis and final results |
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Attachments |
fig 2 |
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No statistical analyses for this end point |
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End point title |
TSH | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
baseline and post-intervention
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Attachments |
figure 1 |
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No statistical analyses for this end point |
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End point title |
fT4 | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
baseline and post-intervention
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Attachments |
figure 1 |
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No statistical analyses for this end point |
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End point title |
T3 | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
baseline and post-intervention
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Attachments |
figure 1 |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Screening - baseline measurement - check up 1 week after intervention - post - intervention measurements.
Participants received information and contact information for when adverse events occured.
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Adverse event reporting additional description |
All AEs will be followed until they have abated, or until a stable situation has been reached.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
Control
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Reporting group description |
- | ||||||||||||||||||||||||||||
Reporting group title |
Hypocaloric dieting
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Reporting group description |
- | ||||||||||||||||||||||||||||
Reporting group title |
Metformin
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Reporting group description |
non serious side effects: minor gastro-intenstinal compaints after starting metfromin treatment. | ||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/30932012 |