Study of Optimal Replacement of Thyroxine in the Elderly (SORTED)

Study of Optimal Replacement of Thyroxine in the Elderly (SORTED) SORTED 1 - a Randomised Controlled Trial (Pilot Study), SORTED 2 - Qualitative Interviews, SORTED 3 - Retrospective Cohort

All patients with hypothyroidism are currently treated the same way, regardless of age. The investigators want to look at whether people aged 80 years or older would benefit from being treated with lower doses of levothyroxine. There are three reasons why the investigators think this could be beneficial, but this is not yet proven:

1. Some older people with hypothyroidism may have few symptoms.
2. Doctors look at the amount of Thyroid Stimulating Hormone (TSH) in the patient's blood to decide the dose of Thyroxine received. The standard "normal" TSH range used to determine the dose of levothyroxine is from younger people. The investigators wonder whether this is appropriate to all age ranges particularly as the investigators know that older people may normally have higher TSH values.
3. If TSH levels are too low there may be a slight increased risk of problems such as brittle bones or an irregular heartbeat.

The best way to test whether older people benefit from lower doses of levothyroxine is by a large clinical trial. Before the investigators can do this, the investigators need to run a smaller clinical trial called a "pilot study" (SORTED 1) to examine whether this is practical and acceptable. The pilot study aims to recruit 50 patients with hypothyroidism aged 80 or above.

Participants will be randomly allocated to receive their routine or lower dose of levothyroxine. Follow-up will be conducted over approximately 25 weeks.

The investigators also propose a qualitative study (SORTED 2) to specifically understand patient's willingness to take part in a RCT and participant's experience of the intervention.

Finally, the investigators propose a retrospective cohort study of 400 treated hypothyroid patients aged 80 years or more registered in 2008 in Primary Care Practices with the aim of studying outcomes after 4 years. The cohort study will collect data required to inform a sample size calculation for a future full study where the primary outcome will be 4 year mortality.

Study Overview

• Status: Completed
• Conditions: Hypothyroidism
• Intervention / Treatment: Drug: Levothyroxine; Drug: Levothyroxine

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Tyne and Wear
    • Gateshead, Tyne and Wear, United Kingdom, NE8 4YL
      • Bensham Hospital
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
      • Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 80 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and Females aged 80 years or older
• Diagnosed with hypothyroidism and treated with Levothyroxine for at least 6 months
• Living independently in the community
• All TSH results within the range 0.4 - 4mU/L in the 3 months before commencing the study
• Participant has provided written informed consent for participation in the study, prior to any study-specific procedures

Exclusion Criteria:

• Established dementia and therefore deemed incapable of providing informed consent.
• Other medical conditions which, inthe opinion of the Chief Investigator, would prevent them from participating in the study (for example, end stage cancer, severe chronic health conditions where the patient is housebound)
• Nursing Homes or Residential Care Home residents
• Individuals with thyroid cancer: since they require high doses of LT4 to suppress their serum TSH
• Individuals on 25 mcg dailty of LT4: dose reduction will mean that they stop thyroid replacement treatment
• Non english speaking individuals
• Participation in any other investigational trials within the last 3 months
• Participants prescribed medications that can affect thyroid function (amiodarone, lithium, carbimazole or propylthiouracil)
• Known or suspected lactose intolerance (this would have implications for the proposed over-encapsulated IMP)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Lower dose of levothyroxine; Participants may be randomised to receive a lower dose of levothyroxine (lower than their usual dose) to achieve a target TSH level of 4.1 - 8.0 mU/L	Drug: Levothyroxine; Participants in the lower dose arm of the study will receive a lower dose of levothyroxine than their usual dose; Drug: Levothyroxine; Participants in the standard dose of treatment will receive their usual dose of levothyroxine
Other: Standard dose of levothyroxine; Patients may be randomised to receive their usual dose of levothyroxine (target TSH level 0.4 - 4.0 mU/L)	Drug: Levothyroxine; Participants in the lower dose arm of the study will receive a lower dose of levothyroxine than their usual dose; Drug: Levothyroxine; Participants in the standard dose of treatment will receive their usual dose of levothyroxine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant's acceptability of study design and willingness to enter study	Participant's acceptability of study design as measured byt he completion rate of participants in each randomised group, as well as their willingness to enter the trial (consented participant to eligible participant approached ratio)	Until completion of recruitment, approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant recruitment rate	As measured by the number of patients randomised divided by the length of the recruitment period. The recruitment period runs from the date that recruitment opened to the date of last randomisation.	Until completion of recruitment, approximately 24 months
Time to achieve desired TSH levels	To review and assess the dose titration strategy (ie reduced LT4 dose or same dose LT4) and length of time required to achieved desired TSH levels (ie number of participants in each group that reach target TSH range at both 12 and 24 weeks)	Until participant completion of SORTED 1 study, approximately within 24 weeks
Medication compliance	Tablet count	For the duration of participant involvment in the study, maximum of 25 weeks
The acceptability of three patient completed questionnaires	The questionnaires include the generic QoL questionnaire (EQ-5D), validated disease-specific QoL questionanaire (ThyDQol) and disease specific hypothyroid-symptom check list (ThySC). The time taken to complete the three questionnaires will be recorded and questionnaire completion rates will be recorded and usefulnesss of questionnaires determined. Any third-party held required in a questionnaire's completion will be recorded.	For the duration of participant involvement in the study, maximum of 25 weeks
Assessment of mobility	Measured by the nurse administered TUG Test, and the FRAT (Falls Risk Assessment Tool)	For the duration of participant involvement in this study, maximum of 25 weeks
Change in specific cardiovascular risk factors	Lipid profile (total cholesterol, HDL, Triglycerides), blood pressure and body weight, and serum results	For the duration of participant involvement in the study, maximum of 25 weeks
Measure of risk of falls	Measure by nurse administrated FRAT (Falls Risk Assessment Tool) test.	For the duration of participant involvement in the study, maximum 25 weeks

Collaborators and Investigators

• Sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
• Collaborators: National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Salman Razvi, Gateshead Health NHS Foundation Trust

Publications and helpful links

General Publications

• Razvi S, Ingoe L, Ryan V, Pearce SH, Wilkes S. Study of Optimal Replacement of Thyroxine in the Elderly (SORTED) - results from the feasibility randomised controlled trial. Thyroid Res. 2016 Oct 10;9:5. doi: 10.1186/s13044-016-0034-x. eCollection 2016.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: July 16, 2012
• First Submitted That Met QC Criteria: July 19, 2012
• First Posted (Estimate): July 24, 2012

Study Record Updates

• Last Update Posted (Estimate): October 12, 2015
• Last Update Submitted That Met QC Criteria: October 7, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hypothyroidism
• Other Study ID Numbers: 5863; PB-PG-0610-22139 (Other Grant/Funding Number: National Institute for Health Research Research for patient Benefit); 2011-004425-27 (EudraCT Number); ISRCTN16043724 (Registry Identifier: ISRCTN)