None listed
Conditions
Brief summary
We plan to study whether combination T4/T3 is better than T4 by itself for individuals who are dissatisfied with T4 alone, and analyse the results at an individual level (ie whether each person benefited or not, rather than whether the whole group benefited or not). If combination T4/T3 treatment improves symptoms of hypothyroidism better than standard T4 treatment, this would become the new standard treatment. On the other hand, if combination treatment is not better than standard treatment, we could conclude this definitively meaning that clinicians and patients would know that this treatment is ineffective, and that patients would not benefit from taking it.
Interventions
Phase 4 n-of-1 trial of four periods of 8 weeks of treatment with either thyroxine and placebo treatment or thyroxine and liothyronine treatment. Each period is separated by a four week period of treatment with thyroxine alone. Each person will have 2 periods of treatment with thyroxine and placebo, and 2 periods of treatment with thyroxine and liothyronine. Thyroxine will be administered in a daily oral dose and liothyronine in a twice daily oral dose, both by capsules. Doses will be individual
Phase 4 n-of-1 trial of four periods of 8 weeks of treatment with either thyroxine and placebo treatment or thyroxine and liothyronine treatment. Each period is separated by a four week period of treatment with thyroxine alone. Each person will have 2 periods of treatment with thyroxine and placebo, and 2 periods of treatment with thyroxine and liothyronine. Thyroxine will be administered in a daily oral dose and liothyronine in a twice daily oral dose, both by capsules. Doses will be individualised for each participant, based on the pre-trial thyroxine dose and subsequently altered during the trial in response to regular (two to four weekly) measurement of thyroid hormone blood levels by an experienced clinician not otherwise involved with the trial. Adherence will be assessed by counting the capsules returned after each treatment period.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adults (over age >18y) with confirmed hypothyroidism defined as previous total thyroidectomy, previous radioiodine treatment with TSH > 4 post radioiodine treatment, or confirmed hypothyroidism with at least two TSH measurements >10 mU/L or at least one TSH measurement >20 mU/L. Individuals with persistent symptoms (>6 months) that are not explained by inadequate treatment of hypothyroidism, low adherence to T4, or other overt co-morbidity and that the individual believes are related to inadequate treatment of hypothyroidism. Eligible individuals will have at symptoms from at least 2 of the following broad groups: tiredness, fatigue, or lethargy (ThyPRO q2); difficult concentrating or thinking, poor memory, or “brain fog” (ThyPRO q3); mood disturbance (ThyPRO q4-6); and bloating or difficulty maintaining weight (ThyPRO 9a). For each broad category, to be eligible individuals must answer “Quite a bit or “Very much” to at least one of the relevant ThyPRO questions. Thyroxine monotherapy for at least 6 months, with measurements of TSH within the normal range for at least the preceding 3 months. Minor abnormalities of TSH (0.2-0.4 or 4-6 mu/L) will not exclude individuals from participating. The thyroxine dose must have been stable for at least the preceding 3 months.
Exclusion criteria
Individuals who are asymptomatic or have symptoms from only 1 of the 4 broad groups outlined in the inclusion criteria or do not meet the criteria for severity of symptoms outlined in the inclusion criteria. Individuals with symptoms they attribute to inadequately treated hypothyroidism that do not fall within the categories outlined in the inclusion criteria. Individuals with poorly controlled hypothyroidism, defined as TSH <0.2 or >6 within the last 3 months. Individuals with significant co-morbidity, in which their symptoms are more likely to be caused by their co-morbidity than hypothyroidism.
Outcome results
None listed