HypothyroidismNCT02467244
Effect of Levothyroxine on Serum Adiponectin, Insulin Resistance and Cardiovascular Risk in Patients With Hypothyroidism
An observational study of Hypothyroidism, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.
Trial summary
The aim of this study is to evaluate plasma adiponectin level, insulin resistance, cardiovascular risk and their correlation (if any) in patients with hypothyroidism and also to investigate the effect of levothyroxine on these parameters. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypothyroidism
- What is being tested?
- Levothyroxine
- How many people
- 120 participants
- Where
- 1 siteIndia
- Study dates
- 1 Feb 2017to 30 Dec 2018
- 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: The study will be conducted on 50 patients of hypothyroidism attending the outpatient department of General Medicine, All India Institute of Medical Sciences, Bhubaneswar. Another 50 euthyroid, age-, sex-matched subjects will be recruited as control.
Who may be able to join
- Patients of either sex, aged 18 years or above suffering from hypothyroidism (hypothyroidism was defined as serum TSH level > 5μIU/ml, serum FT3 level < 1.57 pg/ml, serum FT4 level < 0.7 ng/dL. Subclinical hypothyroidism was defined as an elevated TSH level and a normal serum FT3 and FT4 level) and need treatment (treatment is indicated in patients with TSH levels >10 µIU/mL or in patients with TSH levels between 5 and 10 µIU/mL in conjunction with goiter or positive anti-thyroid peroxidase antibodies (or both).
- Patients not having hepatic/renal dysfunction, Diabetes mellitus, and chronic inflammatory diseases and not taking any medications for thyroid disease.
- Euthyroid subjects not having any significant medical disease.
Who cannot join
- Patients with other comorbidites which can interfere the outcome measures.
- Patients who are already on levothyroxine therapy or taking other medications.
- Patients with subacute thyroiditis were excluded from the study since acute inflammation could influence the measurements.
- Pregnant and lactating mothers.
Trial locations and contacts
1 site in 1 country.
About this study
The aim of this study is to evaluate plasma adiponectin level, insulin resistance, cardiovascular risk and their correlation (if any) in patients with hypothyroidism and also to investigate the effect of levothyroxine on these parameters. The study may explore the lacunae in present treatment protocol and can suggest the possibilities of add-on therapies for a better management.
Read the detailed description
Hypothyroidism is associated with premature atherosclerosis and increased prevalence of coronary artery diseases. Long-term hypothyroidism is associated with severe cardiovascular manifestations including reduced intravascular volume, increased systemic vascular resistance, and hypertension. Hypothyroidism is one of the main causes of secondary dyslipidemia. The classic manifestations of hypothyroidism are raised VLDL, LDL and apo A. The increase in cardiovascular risk is not only due to dyslipidemia, but also to hemodynamic changes, endothelial dysfunction, hormonal and metabolic changes. Insulin resistance and the metabolic syndrome are important cardiovascular risk factors as insulin-resistant individuals with raised TSH have higher LDL concentrations.
Among the various markers associated with obesity and insulin resistance, of particular importance is adiponectin which is inversely related to the degree of adiposity, increases insulin sensitivity, and has antiatherogenic and anti-inflammatory properties, hence may be cardioprotective. Hypoadiponectinaemia is associated with obesity, insulin resistance and type II diabetes, as well as atherosclerosis, hypertension and coronary artery disease.
Treating hypothyroidism with levothyroxine has an antioxidant and cholesterol reducing effect, and thus already has proven beneficial impact on cardiovascular function, blood pressure and lipid profile. But the association of adiponectin and insulin resistance in hypothyroid state and future cardiovascular risk is still not clear because there are few published studies in this domain and result of some the studies are contradictory. The aim of this study is to evaluate plasma adiponectin level, insulin resistance, cardiovascular risk and their correlation (if any) in patients with hypothyroidism and also to investigate the effect of levothyroxine on these parameters.
- Conditions
- Hypothyroidism
- Being tested
- Levothyroxine
- Keywords
- Hypothyroidism, Serum adiponectin, hsCRP, Homeostatic Model Assessment (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI), Cardiovascular risk assessment scoring (Framingham scoring), Levothyroxin
- Medical subject headings
- Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxineDrug
At first visit, after taking detailed history including baseline symptomatology, clinical evaluation, and laboratory investigation, treatment will be started with levothyroxine (50 microgram/day). The dosage of levothyroxine (LT4) will be adjusted (at 4th and 8th week) in an attempt to keep the serum FT4 and TSH concentrations within the normal range. After 12 weeks, all the patients will be followed up, clinical and laboratory tests will be repeated.
| Study group | Role | What they receive |
|---|---|---|
| Euthyroid group | Fifty (50) age and sex matched euthyroid subjects will serve as the control group. Control euthyroid subjects will be evaluated once at baseline and after 12 weeks. | |
| Hypothyroid group | Fifty (50) hypothyroid patients attending the outpatient department of General Medicine, AIIMS, Bhubaneswar, will be recruited for the present study following inclusion and exclusion criteria. Receives: Drug: Levothyroxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of Serum Adiponectin from baseline
Method: ELISA
Measured: At baseline and after 12 weeks at follow up
Change of hsCRP from baseline
Method: ELISA
Measured: At baseline and after 12 weeks at follow up
Change in Insulin resistance from baseline by Homeostatic Model Assessment (HOMA-IR)
Measured: At baseline and after 12 weeks at follow up
Secondary outcomes (8)
Serum Insulin
Method: ELISA
Measured: At baseline and after 12 weeks at follow up
Lipid profile (Total cholesterol)
Measured: At baseline and after 12 weeks at follow up
Lipid profile (LDL-C)
Measured: At baseline and after 12 weeks at follow up
Lipid profile (HDL-C)
Measured: At baseline and after 12 weeks at follow up
Lipid profile (Triglyceride)
Measured: At baseline and after 12 weeks at follow up
Long term glycemic status by Glycosylated hemoglobin (HbA1c%)
Measured: At baseline and after 12 weeks at follow up
Change in Insulin resistance from baseline by Quantitative Insulin Sensitivity Check Index (QUICKI)
Measured: At baseline and after 12 weeks at follow up
Change in Cardiovascular risk assessment scoring (Framingham scoring) from baseline
Measured: At baseline and after 12 weeks at follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2015 (estimated)
- Study start1 Feb 2017
- Primary completion30 Sep 2018
- Study completion30 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences, Bhubaneswar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, RITUPARNA MAITI, All India Institute of Medical Sciences, Bhubaneswar
- Investigators
- DEBASISH HOTA, MD, DM, Study director, AIIMS, Bhubaneswar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02467244
- Sponsor's protocol ID
- T/EM-F/Pharm/14/03
- Status last verified
- Sep 2019
- First submitted
- 4 Jun 2015
- Last updated
- 1 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001 Feb 15;344(7):501-9. doi: 10.1056/NEJM200102153440707. No abstract available.
PubMed 11172193Benvenga S, Robbins J. Lipoprotein-thyroid hormone interactions. Trends Endocrinol Metab. 1993 Aug;4(6):194-8. doi: 10.1016/1043-2760(93)90116-v.
PubMed 18407156Fazio S, Palmieri EA, Lombardi G, Biondi B. Effects of thyroid hormone on the cardiovascular system. Recent Prog Horm Res. 2004;59:31-50. doi: 10.1210/rp.59.1.31.
PubMed 14749496Robinson K, Prins J, Venkatesh B. Clinical review: adiponectin biology and its role in inflammation and critical illness. Crit Care. 2011 Apr 20;15(2):221. doi: 10.1186/cc10021.
PubMed 21586104Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010 Jan 15;314(1):1-16. doi: 10.1016/j.mce.2009.07.031. Epub 2009 Aug 12.
PubMed 19682539Altinova AE, Toruner FB, Akturk M, Bukan N, Cakir N, Ayvaz G, Arslan M. Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism. Clin Endocrinol (Oxf). 2006 Oct;65(4):530-5. doi: 10.1111/j.1365-2265.2006.02628.x.
PubMed 16984248Kowalska I, Borawski J, Nikolajuk A, Budlewski T, Otziomek E, Gorska M, Straczkowski M. Insulin sensitivity, plasma adiponectin and sICAM-1 concentrations in patients with subclinical hypothyroidism: response to levothyroxine therapy. Endocrine. 2011 Aug;40(1):95-101. doi: 10.1007/s12020-011-9446-5. Epub 2011 Mar 18.
PubMed 21424182
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Levothyroxine on Serum Adiponectin, Insulin Resistance and Cardiovascular Risk in Patients With Hypothyroidism
- ClinicalTrials.gov ID
- NCT02467244
- Acronym / sponsor ID
- T/EM-F/Pharm/14/03
- Conditions
- Hypothyroidism
- Keywords
- Hypothyroidism, Serum adiponectin, hsCRP, Homeostatic Model Assessment (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI), Cardiovascular risk assessment scoring (Framingham scoring), Levothyroxin
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- All India Institute of Medical Sciences, BhubaneswarUniversity, hospital or other
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 30 Sep 2018 (actual)
- Study completion
- 30 Dec 2018 (actual)
- First posted
- 10 Jun 2015 (estimated)
- 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.
The aim of this study is to evaluate plasma adiponectin level, insulin resistance, cardiovascular risk and their correlation (if any) in patients with hypothyroidism and also to investigate the effect of levothyroxine on these parameters. The study may explore the lacunae in present treatment protocol and can suggest the possibilities of add-on therapies for a better management.
Detailed description
Hypothyroidism is associated with premature atherosclerosis and increased prevalence of coronary artery diseases. Long-term hypothyroidism is associated with severe cardiovascular manifestations including reduced intravascular volume, increased systemic vascular resistance, and hypertension. Hypothyroidism is one of the main causes of secondary dyslipidemia. The classic manifestations of hypothyroidism are raised VLDL, LDL and apo A. The increase in cardiovascular risk is not only due to dyslipidemia, but also to hemodynamic changes, endothelial dysfunction, hormonal and metabolic changes. Insulin resistance and the metabolic syndrome are important cardiovascular risk factors as insulin-resistant individuals with raised TSH have higher LDL concentrations.
Among the various markers associated with obesity and insulin resistance, of particular importance is adiponectin which is inversely related to the degree of adiposity, increases insulin sensitivity, and has antiatherogenic and anti-inflammatory properties, hence may be cardioprotective. Hypoadiponectinaemia is associated with obesity, insulin resistance and type II diabetes, as well as atherosclerosis, hypertension and coronary artery disease.
Treating hypothyroidism with levothyroxine has an antioxidant and cholesterol reducing effect, and thus already has proven beneficial impact on cardiovascular function, blood pressure and lipid profile. But the association of adiponectin and insulin resistance in hypothyroid state and future cardiovascular risk is still not clear because there are few published studies in this domain and result of some the studies are contradictory. The aim of this study is to evaluate plasma adiponectin level, insulin resistance, cardiovascular risk and their correlation (if any) in patients with hypothyroidism and also to investigate the effect of levothyroxine on these parameters.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Euthyroid group | – | –Fifty (50) age and sex matched euthyroid subjects will serve as the control group. Control euthyroid subjects will be evaluated once at baseline and after 12 weeks. |
| Hypothyroid group | – | Drug: LevothyroxineFifty (50) hypothyroid patients attending the outpatient department of General Medicine, AIIMS, Bhubaneswar, will be recruited for the present study following inclusion and exclusion criteria. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study will be conducted on 50 patients of hypothyroidism attending the outpatient department of General Medicine, All India Institute of Medical Sciences, Bhubaneswar. Another 50 euthyroid, age-, sex-matched subjects will be recruited as control.
Key inclusion criteria (3 listed)
- Patients of either sex, aged 18 years or above suffering from hypothyroidism (hypothyroidism was defined as serum TSH level > 5μIU/ml, serum FT3 level < 1.57 pg/ml, serum FT4 level < 0.7 ng/dL. Subclinical hypothyroidism was defined as an elevated TSH level and a normal serum FT3 and FT4 level) and need treatment (treatment is indicated in patients with TSH levels >10 µIU/mL or in patients with TSH levels between 5 and 10 µIU/mL in conjunction with goiter or positive anti-thyroid peroxidase antibodies (or both).
- Patients not having hepatic/renal dysfunction, Diabetes mellitus, and chronic inflammatory diseases and not taking any medications for thyroid disease.
- Euthyroid subjects not having any significant medical disease.
Key exclusion criteria (4 listed)
- Patients with other comorbidites which can interfere the outcome measures.
- Patients who are already on levothyroxine therapy or taking other medications.
- Patients with subacute thyroiditis were excluded from the study since acute inflammation could influence the measurements.
- Pregnant and lactating mothers.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevothyroxineAt first visit, after taking detailed history including baseline symptomatology, clinical evaluation, and laboratory investigation, treatment will be started with levothyroxine (50 microgram/day). The dosage of levothyroxine (LT4) will be adjusted (at 4th and 8th week) in an attempt to keep the serum FT4 and TSH concentrations within the normal range. After 12 weeks, all the patients will be followed up, clinical and laboratory tests will be repeated. | Drug | Hypothyroid group |
Primary outcome
Change of Serum Adiponectin from baseline
Time frame: At baseline and after 12 weeks at follow up
Method: ELISA
Change of hsCRP from baseline
Time frame: At baseline and after 12 weeks at follow up
Method: ELISA
Change in Insulin resistance from baseline by Homeostatic Model Assessment (HOMA-IR)
Time frame: At baseline and after 12 weeks at follow up
8 secondary outcomes
Serum Insulin
Time frame: At baseline and after 12 weeks at follow up
Lipid profile (Total cholesterol)
Time frame: At baseline and after 12 weeks at follow up
Lipid profile (LDL-C)
Time frame: At baseline and after 12 weeks at follow up
Lipid profile (HDL-C)
Time frame: At baseline and after 12 weeks at follow up
Lipid profile (Triglyceride)
Time frame: At baseline and after 12 weeks at follow up
Long term glycemic status by Glycosylated hemoglobin (HbA1c%)
Time frame: At baseline and after 12 weeks at follow up
Change in Insulin resistance from baseline by Quantitative Insulin Sensitivity Check Index (QUICKI)
Time frame: At baseline and after 12 weeks at follow up
Change in Cardiovascular risk assessment scoring (Framingham scoring) from baseline
Time frame: At baseline and after 12 weeks at follow up
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 1 Oct 2019.
- Results publication: PubMed 11172193Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001 Feb 15;344(7):501-9. doi: 10.1056/NEJM200102153440707. No abstract available.
- Results publication: PubMed 18407156Benvenga S, Robbins J. Lipoprotein-thyroid hormone interactions. Trends Endocrinol Metab. 1993 Aug;4(6):194-8. doi: 10.1016/1043-2760(93)90116-v.
- Results publication: PubMed 14749496Fazio S, Palmieri EA, Lombardi G, Biondi B. Effects of thyroid hormone on the cardiovascular system. Recent Prog Horm Res. 2004;59:31-50. doi: 10.1210/rp.59.1.31.
- Results publication: PubMed 21586104Robinson K, Prins J, Venkatesh B. Clinical review: adiponectin biology and its role in inflammation and critical illness. Crit Care. 2011 Apr 20;15(2):221. doi: 10.1186/cc10021.
- Results publication: PubMed 19682539Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010 Jan 15;314(1):1-16. doi: 10.1016/j.mce.2009.07.031. Epub 2009 Aug 12.
- Results publication: PubMed 16984248Altinova AE, Toruner FB, Akturk M, Bukan N, Cakir N, Ayvaz G, Arslan M. Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism. Clin Endocrinol (Oxf). 2006 Oct;65(4):530-5. doi: 10.1111/j.1365-2265.2006.02628.x.
- Results publication: PubMed 21424182Kowalska I, Borawski J, Nikolajuk A, Budlewski T, Otziomek E, Gorska M, Straczkowski M. Insulin sensitivity, plasma adiponectin and sICAM-1 concentrations in patients with subclinical hypothyroidism: response to levothyroxine therapy. Endocrine. 2011 Aug;40(1):95-101. doi: 10.1007/s12020-011-9446-5. Epub 2011 Mar 18.
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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.
DEBASISH HOTA, MD, DM study director
AIIMS, Bhubaneswar
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, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.
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 3 inclusion and 4 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 1 Oct 2019. 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 India. 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?
Change of Serum Adiponectin from baseline (time frame: At baseline and after 12 weeks at follow up). The study lists 3 primary outcomes in all. 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 NCT02467244, which also lists 7 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 1 Oct 2019.