Thyroxin Treatment in Sub Clinical Hypothyroidism, on the Apnea Hypopnea Index Score, Lipids and Highly Sensitive CRP

Effect of Thyroxin Treatment in Sub Clinical Hypothyroidism Patients, on the Apnea Hypopnea Index Score, Lipid Profiles and Highly Sensitive CRP : A Randomized Double Blind Controlled Trial

Obstructive sleep apnea (OSA) and hypothyroidism are both commonly found in clinical practice, and share a number of symptoms and clinical features. It has been shown that hypothyroid subjects are at high risk of developing sleep disorder breathing and OSA, and adequate thyroxine treatment may reduce the sleep disordered breathing.. However, the time-course and effect of treating subclinical hypothyroidism in OSA patients on the respiratory events during sleep is not known.

Subclinical hypothyroidism is associated with an increased risk of coronary heart disease (CHD). Dyslipidemia is a known complications of subclinical hypothyroidism and the effect of thyroxine treatment on lipid profile is controversial . Some reports suggested higher serum high-sensitivity C-reactive protein (hs-CRP), than healthy subjects; however, the effect of levothyroxine is controversial.

This project will help us to know if the treatment of subclinical hypothyroidism will improve the symptoms and reduce the progression of OSA, which may improve patients' quality of life by reducing the complication of OSA (hypertension, , depression, Cardiovascular diseases, etc.) or may even reduce mortality.It will help us to know the effect of subclinical hypothyroidism treatment on of lipid profiles and hs-CRP.

Study Overview

• Status: Unknown
• Conditions: Dyslipidemia
• Intervention / Treatment: Drug: sugar pill; Drug: levothyroxine

Detailed Description

Research Problem:

Obstructive sleep apnea (OSA) and hypothyroidism are both commonly found in clinical practice, and share a number of symptoms and clinical features. It has been shown that hypothyroid subjects are at high risk of developing sleep disorder breathing and OSA, and adequate thyroxine treatment may reduce the sleep disordered breathing.. However, the time-course and effect of treating subclinical hypothyroidism in OSA patients on the respiratory events during sleep is not known.

Subclinical hypothyroidism is associated with an increased risk of coronary heart disease (CHD). Dyslipidemia is a known complications of subclinical hypothyroidism (2)and the effect of thyroxine treatment on lipid profile is controversial . Some reports suggested higher serum high-sensitivity C-reactive protein (hs-CRP), than healthy subjects ; however, the effect of levothyroxine is controversial .

Research Significance:

This project will help us to know if the treatment of subclinical hypothyroidism will improve the symptoms and reduce the progression of OSA, which may improve patients' quality of life by reducing the complication of OSA (hypertension, , depression, Cardiovascular diseases, etc.) or may even reduce mortality.

It will help us to know the effect of subclinical hypothyroidism treatment on of lipid profiles and hs-CRP.

Research Objectives:

Primary objective:

• Effect of the treatment of subclinical hypothyroidism on the apnea hypopnea index (AHI) score.

Secondary objectives:

• Effect of the treatment of subclinical hypothyroidism on the lipid profile in patient with dyslipidemia.
• Effect of the treatment of subclinical hypothyroidism on hs-CRP

Research Methodology:

Patients with subclinical hypothyroidism will undergo first Polysomnography (PSG) (night 0) and laboratory investigations including lipid profiles and hc-CRP and then they will be enrolled and randomly assigned to receive either levothyroxine replacement therapy or identical placebo tablets in a blinded manner. The starting dose will be 25 mcg/day and the dose will be adjusted every 6 weeks to target TSH level between (0.25 -2.5 IU/mL). We will keep all patients on replacement dose for duration of 24 weeks. PSG will be performed twice only for OSA patient, after 12 weeks (night 1) and after 24 weeks (night 2). Lipid profile and hs-CRP will be done at the end of 24th weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia, 11472
    • Recruiting
    • University Sleep Disorders Center
    • Contact: Anwar A Jammah, MD, FACP,FRCPC; Phone Number: (+966 1) 467-11784; 467-9179; Email: drjammah@gmail.com
    • Contact: Reda AboAlsoud, MD; Phone Number: +966509662742; Email: usdc@ksu.edu.sa
    • Sub-Investigator: Ahmed S BaHammam, FRCP, FCCP
    • Principal Investigator: Anwar A Jammah, MD, FACP, FRCPC
    • Sub-Investigator: Muneer S Muhammad

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients >18 years old
• With Subclinical hypothyroidism defined as serum TSH concentration above 5.0 IU/mL when serum FT4 level is within the reference range
• With OSA defined as mild OSA: AHI 5 to 15/h; moderate OSA:AHI 15 to 30/h; and severe OSA: AHI greater than 30/h (30) will be enrolled.
• With confirmed sustained subclinical hypothyroidism, thus excluding patients with a temporary condition such as that in recovery from a non-thyroidal illness, measurement of TSH and FT4 will be conducted within four weeks before randomization.

Exclusion Criteria:

• Current treatment with Levothyroxine and lipid lowering medications or within two months before randomization.
• Conditions known to cause dyslipidemia e.g. uncontrolled diabetes mellitus (HbA1c >9), alcoholism and some medication use e.g. Estrogens. Glucocorticoids, Retinoids or Interferons.
• Conditions indicating levothyroxine treatment (34); including TSH levels more than 10 mU/l, clear symptoms or signs associated with thyroid failure and not related to OSA . e.g. goiter.
• State of pregnancy, Breast feeding or allergy to levothyroxine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: sugar pill	Drug: sugar pill; Eligible patients will be randomized and be given 25 mcg of levothyroxine or identical placebo tablet at the beginning of the enrollment. The dosage of drug will subsequently be individualized for each patients according to Serum levels of TSH and FT4 which will be checked initially and then every 6 weeks until the end of the study. The investigators will attempt to maintain TSH levels between (0.25-2.5) mU/l which is the lower half of normal range by adding or reducing the dose of medication. Advice given to patient regarding whether to increase or decrease the dose of medications will be based on patient TSH level according to study protocol.
Active Comparator: Levothyroxine; Eligible patients will be randomized and be given 25 mcg of levothyroxine or identical placebo tablet at the beginning of the enrollment. The dosage of levothyroxine will subsequently be individualized for each patients. Serum levels of TSH and FT4 will be checked initially and then every 6 weeks until the end of the study. The investigators will attempt to maintain TSH levels between (0.25-2.5) mU/l which is the lower half of normal range. Advice given to patient regarding whether to increase or decrease the dose of medications will be based on patient TSH level according to study protocol.	Drug: levothyroxine; Eligible patients will be randomized and be given 25 mcg of levothyroxine or identical placebo tablet at the beginning of the enrollment. The dosage of levothyroxine will subsequently be individualized for each patients according to Serum levels of TSH and FT4 which will be checked initially and then every 6 weeks until the end of the study. The investigators will attempt to maintain TSH levels between (0.25-2.5) mU/l which is the lower half of normal range by adding or reducing the dose of levothyroxine. Advice given to patient regarding whether to increase or decrease the dose of medications will be based on patient TSH level according to study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of the treatment of subclinical hypothyroidism on the apnea hypopnea index (AHI) score.	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of the treatment of subclinical hypothyroidism on the lipid profile in patient with dyslipidemia and on hs-CRP	24 weeks

Collaborators and Investigators

• Sponsor: King Saud University

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): October 1, 2013

Study Registration Dates

• First Submitted: December 3, 2011
• First Submitted That Met QC Criteria: December 5, 2011
• First Posted (Estimate): December 6, 2011

Study Record Updates

• Last Update Posted (Estimate): December 8, 2011
• Last Update Submitted That Met QC Criteria: December 6, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: focus of study instead
• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Endocrine System Diseases; Thyroid Diseases; Lipid Metabolism Disorders; Hypersensitivity; Hypothyroidism; Dyslipidemias
• Other Study ID Numbers: E-11-465