The TRUST Study - Depression Substudy

NCT01853579 | Completed Phase 4 DMC

• 3 other identifiers: 162/112011-004554-2601660126
• Study Type: interventional
• Target: 426
• Locations: 2 countries
• Sites: 3

Brief Summary

Mild thyroid failure is a common condition among older adults and has been associated with numerous adverse effects on health, such as cardiovascular disease, cognition disturbances and muscular problems. Mild thyroid failure has also been associated with an increased risk of developing depression. To date, only few studies have investigated the effect of thyroid hormone replacement on depression in patients with mild thyroid failure. This study therefore aims to assess whether thyroid hormone replacement in older adults with mild thyroid failure is associated with a decrease in the presence of depressive symptoms. This study forms a substudy of a large international study on thyroid hormone replacement in older adults with mild thyroid failure (the TRUST study).

Conditions

Subclinical Hypothyroidism; Depression

Keywords

Randomized controlled trial; Subclinical hypothyroidism; Levothyroxine; Depression

Outcome Measures

Primary Outcomes (1)

• Change from baseline in 15-items Geriatric Depression Scale

  At 1 Year

Study Arms (2)

1

EXPERIMENTAL

Experimental: Drug: Levothyroxine The intervention will start with Levothyroxine 50 mcg daily (reduced to 25 mcg in subjects \<50 kg of body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) vs. matching placebo; at 3 months, if the serum TSH level is \<0.4 mU/L, dose will be reduced by 25 mcg; TSH \>=0.4 and \<4.6 mU/L, no change to dose; TSH \>=4.6 mU/L, additional 25 mcg. The process will be repeated at 12 months, then annually; mock titration will be performed in the placebo group. The maximum possible dose of Levothyroxine which will be prescribed is 150 mcg (after 4 increments of 25 mcg at 3 months, 1, 2, 3 years; from the starting dose of 50 mcg).

Drug: Levothyroxine

2

PLACEBO COMPARATOR

Placebo Comparator: Drug: Placebo Control patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug. Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg.

Drug: Placebo

Interventions

Levothyroxine DRUG

The intervention will start with Levothyroxine 50 µg daily (reduced to 25 µg in subjects \<50Kg body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) versus matching placebo; at 3 months if the serum TSH level is \<0.4 mU/L dose will be reduced by 25 µg; TSH \>=0.4 and \<4.6 mU/L, no change to dose; TSH \>=4.6mUL, additional 25 µg. The process will be repeated at 12 months then annually. Mock titration will be performed in the placebo group. The maximum possible dose of Levothyroxine that will be prescribed is 150μg (after 4 increments of 25μg at 3 months, 1, 2 and 3 years; from the starting dose of 50μg).

1

Placebo DRUG

Control patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug. Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg.

2

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Community-dwelling patients aged \>= 65 years with subclinical hypothyroidism
• Written informed consent

You may not qualify if:

• Subjects currently on Levothyroxine or antithyroid drugs, amiodarone or lithium
• Recent thyroid surgery or radio-iodine (within 12 months)
• Grade IV NYHA heart failure
• Prior clinical diagnosis of dementia
• Recent hospitalisation for major illness or elective surgery (within 4 weeks)
• Terminal illness
• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
• Subjects who are participating in ongoing RCTs of therapeutic interventions (including CTIMPs)
• Plan to move out of the region in which the trial is being conducted within the next 2 years (proposed minimum follow-up period)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Leiden University Medical Center: collaborator
• University of Bern: collaborator

Study Sites (3)

Leiden University Medical Center

Leiden, 2300, Netherlands

Location

Department of General Internal Medicine

Lausanne, Canton of Vaud, 1011, Switzerland

Location

University Clinic for General Internal Medicine, Bern University Hospital

Bern, 3010, Switzerland

Location

Related Publications (1)

• Wildisen L, Feller M, Del Giovane C, Moutzouri E, Du Puy RS, Mooijaart SP, Collet TH, Poortvliet RKE, Kearney P, Quinn TJ, Kloppel S, Bauer DC, Peeters RP, Westendorp R, Aujesky D, Gussekloo J, Rodondi N. Effect of Levothyroxine Therapy on the Development of Depressive Symptoms in Older Adults With Subclinical Hypothyroidism: An Ancillary Study of a Randomized Clinical Trial. JAMA Netw Open. 2021 Feb 1;4(2):e2036645. doi: 10.1001/jamanetworkopen.2020.36645.

  PMID: 33566107 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Nicolas Rodondi, MD, MAS

  University Clinic of General Internal Medicine, Bern University Hospital, Bern, Switzerland

  PRINCIPAL INVESTIGATOR

• Jacobijn Gussekloo, MD

  Leiden University Medical Center, Leiden, The Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2013
• First Posted: May 15, 2013
• Study Start: March 1, 2013
• Primary Completion: April 5, 2018
• Study Completion: April 5, 2018
• Last Updated: June 14, 2018

Record last verified: 2018-06

Locations

NL (1); CH (2)