|- candidate number||24331|
|- NTR Number||NTR5853|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||10-mei-2016|
|- Secondary IDs||NL56309.091.16 |
|- Public Title||The influence of metformin and a hypocaloric diet on thyroid radioactive iodide uptake in healthy volunteers: a pilot study|
|- Scientific Title||The influence of metformin and a hypocaloric diet on thyroid radioactive iodide uptake in healthy volunteers: a pilot study|
|- ACRONYM||thyroid iodide uptake study 1|
|- hypothesis||use of metformin and a hypocaloric diet result in reduced thyroid iodide uptake. |
|- Healt Condition(s) or Problem(s) studied||Thyroid disease|
|- Inclusion criteria||. male|
. No mental illness
. lnformed consent
. Healthy, specifically no history of thyroid disease or renal insufficiency
. Aged between 18-50 years
. Normal weight (BMl: '18.5-25.0 kg/m2)
. Maintained stable body weight for previous 6 months
|- Exclusion criteria||. Mentally incompetent|
. Any thyroid condition: hypo- or hyperthyroidism, thyroid cancer, other thyroid conditions.
. Any chronic illness, including diabetes mellitus, acute or chronic infections, other disease requiring treatment.
. Use of any medication or homeopathic medications. Use of paracetamol is allowed.
. Previous radioactive iodide scanning or other imaging techniques with administration of iodide containing
contrast fluids within 6 months
. Use of supplements that contain large quantities of iodide
. Structural alcohol intake > 3 glasses/day
. Subjects who have taken part in any drug trial within 3 months prior start of this study.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||9-mei-2016|
|- planned closingdate||1-mei-2017|
|- Target number of participants||17|
|- Interventions||group1: 2 week course of metformin and iodide restricted diet|
Group 2: 2 week course of hypocaloric, iodide restricted diet
Groep 3 (control group): 2 week course of iodide restricted diet
|- Primary outcome||Thyroid I-123 uptake. |
|- Secondary outcome||thyroid function in terms of TSH, fT4 and T3 measurements.|
|- Timepoints||- 2 week course of iodide restricted diet, followed by baseline measurements of thyroid function and thyroid radioactive iodide uptake|
- 2 week intervention period, followed by measurements of thyroid function and thyroid radioactive iodide uptake after intervention
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Drs. Yvette Sloot|
|- CONTACT for SCIENTIFIC QUERIES||Drs. Yvette Sloot|
|- Sponsor/Initiator ||Radboud University Medical Center Nijmegen|
(Source(s) of Monetary or Material Support)
|- Brief summary||Rationale: Treatment with radioactive iodide (RAI) is a widely used and highly efficient treatment for
benign and malignant thyroid diseases, such as differentiated thyroid cancer (TC). Specific thyroid
iodide uptake is needed to assure effective RAI treatment in TC, which is facilitated by the expression
of a sodium-iodide symporter (NIS) on the thyroid cell. Factors that influence either positively or
negatively the NIS expression and function could affect the response to RAI treatment. It has been
shown that that activation of AMP-activated- protein-kinase (AMPK) leads to decreased NIS
expression and iodide uptake in in vitro studies and animal models. For this reason we will focus in
this study on modulators of AMPK activity in relation to thyroid iodide uptake in humans. The first
important modulator of AMPK is metformin, a well known drug in the treatment of type 2 diabetes
mellitus (DM). Because there is evidence that thyroid disease and DM are closely linked and
metformin is investigated as important adjunct in the treatment of TC, we estimate that there is a
large group of patients that use metformin who undergo RAI treatment, making it interesting to
investigate the effects of metfromin on thyroid iodide uptake. Secondly, we want to investigate the
effects of a hypocaloric diet, since hypocaloric conditions also induce AMPK activation. During RAI
treatment for TC, patients undergo thyroid hormone withdrawal or administration of rhTSH to
stimulated thyroid iodide uptake. Thyroid hormone withdrawal results in symptomatic
hypothyroidism, leading to complaints such as weight gain and nausea, which could result in reduced
food intake and thus hypocaloric conditions. Since this could influence AMPK activation and thus
thyroid iodide uptake and RAI efficacy, it is relevant to investigate the effect of altered caloric intake
on thyroid iodide uptake.
Objective: To assess the physiological effects of metformin and hypocaloric dieting on thyroid iodide
uptake and thyroid function in healthy volunteers.
Study design: This is an investigator initiated interventional pilot study.
Study population: 17 healthy male volunteers, aged 18-50 years.
Intervention: The first group of 7 subjects will follow a two week course of metformin according a
specific dosing scheme and follow an iodide restricted diet. Group 2 with 7 subjects will follow a
hypocaloric diet (40% caloric restriction, high fat, low carbohydrate content) with an iodide restricted
diet for two weeks. There will be a control group of 3 subjects to assess the degree of intra-
individual variation in thyroid iodide uptake, who will only follow a iodide restricted diet.
Main study parameters/endpoints: Primary endpoint is the change observed in 123 I thyroid uptake
measured by Radioactive iodide uptake testing (RAIU) before and after either metformin or
hypocaloric dieting. Secondary endpoints are the changes in serum levels of TSH, fT4 and T3 before
and after intervention.
|- Main changes (audit trail)||16-sept-2016:
Participants are no longer required to follow a strict iodide restricted diet. Instead, participants will be instructed to avoid using certain products which contain large amounts of iodide during the study. This setup is more in accordance with clinical practice. |
|- RECORD||10-mei-2016 - 16-sep-2016|