HypothyroidismBrainGABANCT06649318
Effect of Brain GABA Metabolite Amount to Propofol Utilisation Under TIVA in Hypothyroid Patient
An observational study of Hypothyroidism and Anesthesia, General, run by Duzce University at 1 site in Turkey (Türkiye).
Trial summary
Introduction: GABAergic synaptic transmigration in the anterior cingulate (ACC) cortex of hypothyroid rats has been demonstrated by electrophysiologic recordings. In this study, the investigators primary aim was to determine whether the dose requirement of propofol used under the guidance of bispectral index… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypothyroidism, Anesthesia, General, Propofol Dosage
- How many people
- 80 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 23 Jun 2023to 1 Oct 2024
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients ASAI-II status, older than 18 years and younger than 65 years who will be operated under total intravenous anesthesia
Who may be able to join
- Patients older than 18 years and younger than 65 years who will be operated under total intravenous anesthesia
- ASAI-II status
Who cannot join
- Patients for whom Intensive Care Unit (ICU) indication is foreseen
- Chronic obstructive pulmonary disease,
- A personal or family history of malignant hyperthermia,
- Alcohol or drug addiction,
- History of liver or kidney disease,
- With coronary artery disease or heart failure,
Show all 14Show fewer
- Significant anemia or hemoglobinopathy,
- Hypotension, hypovolemia, sepsis,
- Unregulated diabetic patients,
- Female patients who are pregnant or lactating.
- Allergic to propofol and halogens
- Patients on gabapentinoids
- Those with a history of head trauma
- Those with neurological disorders
Trial locations and contacts
1 site in 1 country.
About this study
Introduction: GABAergic synaptic transmigration in the anterior cingulate (ACC) cortex of hypothyroid rats has been demonstrated by electrophysiologic recordings. In this study, the investigators primary aim was to determine whether the dose requirement of propofol used under the guidance of bispectral index monitoring is correlated with thyroid hormone levels in patients undergoing surgery under total intravenous anaesthesia.The investigators secondary aim was to determine whether there is a difference in the amount of GABA metabolite in the midline posterior (mPCC) and midline anterior cingulate cortex (mACC) region in normal and thyroid dysfunction patients on magnetic resonance spectroscopic imaging.
Method: After ethics committee approval, the study included patients with ASA I-II status: Group 1 (Control group n=40) patients with regular thyroid function tests and Group 2 (Hypothyroid group n=40) patients with hypothyroidism history with Levothyroxine sodium treated. Patients were evaluated preoperatively with the Montreal assessment scale and Beck anxiety scale. Written informed consent was obtained from all the patients, andparticipants underwent a brain MRI examination one day before the operation. The possible increase of GABA, which is present in the imaging with NAA, Cr and Glx in the range of 2.2-2.4 ppm, was recorded as an elevated spectral curve in the MR spectroscopy spectrum and its numerical equivalent was determined as the amount of chemical shifting in the y-axis. To determine GABA, the investigators set the sequence with optimal parameters, for which the investigators set the radio frequency pulse-echo time (TE) as 20 msec.The investigators set the voxel size as 2*3*3 cm to obtain optimal results. Researchers determined single voxel imaging MR spectroscopy sampling area in the midline anterior and posterior to the cingulate gyrus in all patients. Patients with spectral voxels outside the specified area, dense ventricular contamination within the voxel, or with intra-voxel dense ventricular contamination or seminal contamination were excluded from the study.
Patients were operated on under total intravenous anaesthesia. Anesthesia Induction was performed with 2 mg/kg propofol, 0.5 mg/kg fentanyl and 0.5 mg/kg rocuronium. Maintenance was achieved by bispectral index monitoring with propofol infusion at a dose of 1-8 mg/kg/min and remifentanil infusion at a dose of 0.5-2 mcg/kg/min with values between 40-60.
Read the detailed description
It is generally accepted that thyroid hormones have important effects on the normal functioning of the adult brain. Hypothyroidism is a common endocrine disorder characterized by low secretion of thyroid hormone. It is often associated with cognitive and neuropsychiatric changes. Multimodal imaging studies have demonstrated structural and functional changes in the brain in patients with hypothyroidism. Publications have reported decreased hippocampal area, microstructural changes in brain white matter, changes in brain metabolic rate, decreased regional blood flow, decreased cerebral glucose metabolism, decreased functional connectivity and decreased cortical excitability.
It is noteworthy that the hormone affects GABAergic neurotransmission. Preclinical studies have shown that T3 and T4 hormones modulate GABA receptor activity. Recent studies in rat hippocampus have shown a decrease in GABA levels in the hippocampus in the hypothyroid group. Anesthetic drugs that researchers use as daily routine anesthetic applications in the clinic for general anesthesia mostly show their effects through GABA receptors. Therefore, the investigators argue that in thyroid hormone disorders, which are effective on the GABAergic system, the need for anesthetic substances routinely used during general anesthesia may vary compared to patients with normal thyroid function.
The investigators study, they aimed to observe whether there is a difference between the anesthetic substance requirements of patients with normal thyroid function and hypothyroid patients under general anesthesia with monitoring. The researchers also aimed to observe whether there is a regional difference in non-contrast MR spectroscopic evaluation in patients with normal and low thyroid dysfunction. There were no invasive procedures in the investigators study.
- Conditions
- Hypothyroidism, Anesthesia, General, Propofol Dosage, Magnetic Resonance Imaging (MRI), Remifentanil, Gamma Aminobutyric Acid
- Keywords
- Hypothyroid patient, GABA metabolites, Magnetic resonance spectroscopy screening, propofol, remifentanyl, anesthesia
- Medical subject headings
- Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Control group (n=40) Patients with normal thyroid function tests | |
| Group 2 | Hypothyroid patients group (n=40) . Hypothyroid and treated with Levothyroxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes of participants' thyroid hormone levels measured before anesthesia and doses of propofol and remifentanil used in total intravenous anesthesia under bispectral index monitoring.
The difference of participants' thyroid hormone levels (IU/mL) before anesthesia and compare the doses of propofol in miligram and remifentanil in microgram used in total intravenous anesthesia under bispectral index monitoring.
Measured: From enrollment to the end of treatment at 1 day
Secondary outcomes (1)
Changes in the amounts of brain GABA metabolites chemical shifts measured in ppm units between participants with hypothyroidism and participants with normal thyroid function before anesthesia. .
To determine whether there is a difference in the amount of GABA metabolite in the midline posterior (mPCC) and midline anterior cingulate cortex (mACC) region in normal and thyroid dysfunction patients on magnetic resonance spectroscopic imaging and its correlation of the propofol and remifentanil needing.
Measured: From enrollment to the end of treatment at 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2024
- Study start23 Jun 2023
- Primary completion1 Aug 2024
- Study completion1 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HypothyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 80 participants (actual)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Duzce University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06649318
- Sponsor's protocol ID
- 2023-117
- Acronym
- BrainGABA
- Status last verified
- Mar 2025
- First submitted
- 17 Oct 2024
- Last updated
- 19 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Fu X, Sun P, Zhang X, Zhu D, Qin Q, Lu J, Wang J. GABA in the anterior cingulate cortex mediates the association of white matter hyperintensities with executive function: a magnetic resonance spectroscopy study. Aging (Albany NY). 2024 Mar 1;16(5):4282-4298. doi: 10.18632/aging.205585. Epub 2024 Mar 1.
PubMed 38441529Yi J, Zheng JY, Zhang W, Wang S, Yang ZF, Dou KF. Decreased pain threshold and enhanced synaptic transmission in the anterior cingulate cortex of experimental hypothyroidism mice. Mol Pain. 2014 Jun 18;10:38. doi: 10.1186/1744-8069-10-38.
PubMed 24943008Brohan J, Goudra BG. The Role of GABA Receptor Agonists in Anesthesia and Sedation. CNS Drugs. 2017 Oct;31(10):845-856. doi: 10.1007/s40263-017-0463-7.
PubMed 29039138
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Brain GABA Metabolite Amount to Propofol Utilisation Under TIVA in Hypothyroid Patient
- ClinicalTrials.gov ID
- NCT06649318
- Acronym / sponsor ID
- BrainGABA / 2023-117
- Conditions
- Hypothyroidism, Anesthesia, General, Propofol Dosage, Magnetic Resonance Imaging (MRI), Remifentanil, Gamma Aminobutyric Acid
- Keywords
- Hypothyroid patient, GABA metabolites, Magnetic resonance spectroscopy screening, propofol, remifentanyl, anesthesia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Duzce UniversityUniversity, hospital or other
- Study start
- 23 Jun 2023 (actual)
- Primary completion
- 1 Aug 2024 (actual)
- Study completion
- 1 Oct 2024 (actual)
- First posted
- 18 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Introduction: GABAergic synaptic transmigration in the anterior cingulate (ACC) cortex of hypothyroid rats has been demonstrated by electrophysiologic recordings. In this study, the investigators primary aim was to determine whether the dose requirement of propofol used under the guidance of bispectral index monitoring is correlated with thyroid hormone levels in patients undergoing surgery under total intravenous anaesthesia.The investigators secondary aim was to determine whether there is a difference in the amount of GABA metabolite in the midline posterior (mPCC) and midline anterior cingulate cortex (mACC) region in normal and thyroid dysfunction patients on magnetic resonance spectroscopic imaging.
Method: After ethics committee approval, the study included patients with ASA I-II status: Group 1 (Control group n=40) patients with regular thyroid function tests and Group 2 (Hypothyroid group n=40) patients with hypothyroidism history with Levothyroxine sodium treated. Patients were evaluated preoperatively with the Montreal assessment scale and Beck anxiety scale. Written informed consent was obtained from all the patients, andparticipants underwent a brain MRI examination one day before the operation. The possible increase of GABA, which is present in the imaging with NAA, Cr and Glx in the range of 2.2-2.4 ppm, was recorded as an elevated spectral curve in the MR spectroscopy spectrum and its numerical equivalent was determined as the amount of chemical shifting in the y-axis. To determine GABA, the investigators set the sequence with optimal parameters, for which the investigators set the radio frequency pulse-echo time (TE) as 20 msec.The investigators set the voxel size as 2*3*3 cm to obtain optimal results. Researchers determined single voxel imaging MR spectroscopy sampling area in the midline anterior and posterior to the cingulate gyrus in all patients. Patients with spectral voxels outside the specified area, dense ventricular contamination within the voxel, or with intra-voxel dense ventricular contamination or seminal contamination were excluded from the study.
Patients were operated on under total intravenous anaesthesia. Anesthesia Induction was performed with 2 mg/kg propofol, 0.5 mg/kg fentanyl and 0.5 mg/kg rocuronium. Maintenance was achieved by bispectral index monitoring with propofol infusion at a dose of 1-8 mg/kg/min and remifentanil infusion at a dose of 0.5-2 mcg/kg/min with values between 40-60.
Detailed description
It is generally accepted that thyroid hormones have important effects on the normal functioning of the adult brain. Hypothyroidism is a common endocrine disorder characterized by low secretion of thyroid hormone. It is often associated with cognitive and neuropsychiatric changes. Multimodal imaging studies have demonstrated structural and functional changes in the brain in patients with hypothyroidism. Publications have reported decreased hippocampal area, microstructural changes in brain white matter, changes in brain metabolic rate, decreased regional blood flow, decreased cerebral glucose metabolism, decreased functional connectivity and decreased cortical excitability.
It is noteworthy that the hormone affects GABAergic neurotransmission. Preclinical studies have shown that T3 and T4 hormones modulate GABA receptor activity. Recent studies in rat hippocampus have shown a decrease in GABA levels in the hippocampus in the hypothyroid group. Anesthetic drugs that researchers use as daily routine anesthetic applications in the clinic for general anesthesia mostly show their effects through GABA receptors. Therefore, the investigators argue that in thyroid hormone disorders, which are effective on the GABAergic system, the need for anesthetic substances routinely used during general anesthesia may vary compared to patients with normal thyroid function.
The investigators study, they aimed to observe whether there is a difference between the anesthetic substance requirements of patients with normal thyroid function and hypothyroid patients under general anesthesia with monitoring. The researchers also aimed to observe whether there is a regional difference in non-contrast MR spectroscopic evaluation in patients with normal and low thyroid dysfunction. There were no invasive procedures in the investigators study.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 1 Day
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | –Control group (n=40) Patients with normal thyroid function tests |
| Group 2 | – | –Hypothyroid patients group (n=40) . Hypothyroid and treated with Levothyroxine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients ASAI-II status, older than 18 years and younger than 65 years who will be operated under total intravenous anesthesia
Key inclusion criteria (2 listed)
- Patients older than 18 years and younger than 65 years who will be operated under total intravenous anesthesia
- ASAI-II status
Key exclusion criteria (14 listed)
- Patients for whom Intensive Care Unit (ICU) indication is foreseen
- Chronic obstructive pulmonary disease,
- A personal or family history of malignant hyperthermia,
- Alcohol or drug addiction,
- History of liver or kidney disease,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Changes of participants' thyroid hormone levels measured before anesthesia and doses of propofol and remifentanil used in total intravenous anesthesia under bispectral index monitoring.
Time frame: From enrollment to the end of treatment at 1 day
The difference of participants' thyroid hormone levels (IU/mL) before anesthesia and compare the doses of propofol in miligram and remifentanil in microgram used in total intravenous anesthesia under bispectral index monitoring.
1 secondary outcome
Changes in the amounts of brain GABA metabolites chemical shifts measured in ppm units between participants with hypothyroidism and participants with normal thyroid function before anesthesia. .
Time frame: From enrollment to the end of treatment at 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
- Background: PubMed 38441529Fu X, Sun P, Zhang X, Zhu D, Qin Q, Lu J, Wang J. GABA in the anterior cingulate cortex mediates the association of white matter hyperintensities with executive function: a magnetic resonance spectroscopy study. Aging (Albany NY). 2024 Mar 1;16(5):4282-4298. doi: 10.18632/aging.205585. Epub 2024 Mar 1.
- Background: PubMed 24943008Yi J, Zheng JY, Zhang W, Wang S, Yang ZF, Dou KF. Decreased pain threshold and enhanced synaptic transmission in the anterior cingulate cortex of experimental hypothyroidism mice. Mol Pain. 2014 Jun 18;10:38. doi: 10.1186/1744-8069-10-38.
- Results publication: PubMed 29039138Brohan J, Goudra BG. The Role of GABA Receptor Agonists in Anesthesia and Sedation. CNS Drugs. 2017 Oct;31(10):845-856. doi: 10.1007/s40263-017-0463-7.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypothyroidism and Anesthesia, General, run by Duzce University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes of participants' thyroid hormone levels measured before anesthesia and doses of propofol and remifentanil used in total intravenous anesthesia under bispectral index monitoring. (time frame: From enrollment to the end of treatment at 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06649318, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2025.