A Clinical Trial of Adjunctive Thyroxine for Avolition in Schizophrenia

NCT07011953 | Not Yet Recruiting Early Phase 1

• 1 other identifier: 2025-06-02
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to investigate whether adjunctive thyroxine treatment can ameliorate motivation deficits in adults with schizophrenia experiencing predominant avolition (core negative symptom). The main questions it aims to answer are:

• Does adjunctive thyroxine reduce avolition symptoms compared to placebo?
• Does adjunctive thyroxine normalize cortico-striatal circuit activity during reward processing? Researchers will compare the treatment group (adjunctive sodium tablets, 50μg/day) with the control group (dose-equivalent placebo starch tablet) to see if thyroid hormone:
• Significantly improves clinical scores of avolition
• Modulates neural activation in motivation-processing brain circuits
• Maintain stable antipsychotic therapy for 8 weeks
• Receive daily levothyroxine/placebo tablets
• Complete the following assessments pre-/post-treatment:
• Clinical evaluations (PANSS, NSA, PSP)
• MRI scans (resting-state, structural, fMRI during reward tasks)
• Blood tests
• Behavioral motivation tasks

Conditions

Schizophrenia; Avolition

Keywords

schizophrenia; avolition; thyroxine; double blind; randomized controlled trial; motivation

Outcome Measures

Primary Outcomes (1)

• the score of Motivation subscale of the Negative Symptom Assessment (NSA-15)

  Baseline, 2-week follow-up, 4-week follow-up, 6-week follow-up, 8-week follow-up

Secondary Outcomes (3)

• Motivational deficits(avolition) measured by N2 (Emotional Withdrawal) and N4 (Passive/Apathetic, Social Withdrawal) items in the Positive and Negative Syndrome Scale (PANSS).

  Baseline, 2-week follow-up, 4-week follow-up, 6-week follow-up, 8-week follow-up

• Performance of the monetary incentive delay task (MID)

  baseline, 8-week follow-up

• Performance of the Effort-Expenditure for Rewards Task (EEfRT)

  baseline, 8-week follow-up

Study Arms (2)

Treatment group: adjunctive thyroxine

EXPERIMENTAL

Maintain the original antipsychotic regimen combined with levothyroxine sodium tablets (Euthyrox), 50 μg/day for 8 weeks. Manufacturer: Merck Serono Ltd.

Drug: Antipsychotics plus Levothyroxine Sodium

Placebo Control group

PLACEBO COMPARATOR

The placebo control group will maintain the original antipsychotic regimen, supplemented with a dose-equivalent placebo tablet (starch tablet) matching levothyroxine sodium in appearance and nominal dosage (50 μg/day) for 8 weeks. Manufacturer: Boji Medical Technology Co., Ltd.

Drug: Antipsychotics plus Placebo

Interventions

Antipsychotics plus Levothyroxine Sodium DRUG

Maintain the original antipsychotic regimen combined with levothyroxine sodium tablets (Euthyrox), 50 μg/day for 8 weeks. Manufacturer: Merck Serono Ltd. Levothyroxine Sodium Tablets should be administered as a single daily dose on an empty stomach, 30 minutes before breakfast, with sufficient liquid (e.g., half a glass of water).

Treatment group: adjunctive thyroxine

Antipsychotics plus Placebo DRUG

All participants maintain pre-study antipsychotic medication at stable doses. ADDITIONALLY, they receive a visually identical placebo tablet. Placebo characteristics \& Blinding guaranteet: Matches levothyroxine in appearance (size/color/coating), taste, and packaging. Active ingredien : starch tablet with no biological activity. Administration: Once daily in the morning under identical fasting conditions.

Placebo Control group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Meet the diagnostic criteria for schizophrenia according to the International Classification of Diseases, 10th Revision (ICD-10) (World Health Organization, 1993);
• Aged between 18 and 45 years, right-handed;
• Currently clinically stable, with the primary antipsychotic medication formulation and dosage unchanged for at least 4 weeks, and a total PANSS score ≤ 60;
• Predominant avolition symptoms, defined as a score ≥ 16 on the Motivation subscale of the Negative Symptom Assessment (NSA-15) (Zhou et al., 2023), with fewer than 3 items scoring ≥ 4 and fewer than 2 items scoring ≥ 5 on the PANSS positive subscale (Rabinowitz et al., 2013);
• Receiving one or two second-generation antipsychotics (SGAs), with stable medication doses for at least 1 month;
• Willingness and ability to maintain stable medication doses throughout the trial period;
• Capacity to understand study procedures, cooperate with all testing requirements, and provide written informed consent.

You may not qualify if:

• Current treatment with clozapine or first-generation antipsychotics;
• Current use of thyroid hormone medications or presence of thyroid dysfunction;
• Hypersensitivity to levothyroxine sodium; or history of non-hypothyroid-related heart failure, tachyarrhythmias, or recent myocardial infarction;
• Current use of medications known to interact with levothyroxine sodium that may affect its efficacy or safety (e.g., antidiabetic drugs, coumarin derivatives);
• History of endocrinological or cardiovascular/cerebrovascular diseases;
• IQ \< 80 assessed by the Chinese short-form Wechsler Adult Intelligence Scale (Gong, 1981);
• History of substance abuse or drug addiction;
• History of traumatic brain injury or neurological disorders;
• Receiving electroconvulsive therapy (ECT) within the last 3 months;
• Pregnancy, lactation, or planning pregnancy within the next 2 months (for female participants);
• Claustrophobia; implanted metal devices (e.g., prosthetic implants, pacemakers); or other contraindications to MRI scanning.

Sponsors & Collaborators

• Peking University: lead

MeSH Terms

Conditions

Schizophrenia

Interventions

Antipsychotic Agents; Thyroxine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Psychotropic Drugs; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: June 10, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: June 10, 2025

Record last verified: 2025-06