T3-4-Hypo trial - Netherlands

[helvella]

Do view the original which includes a map and various links.

16 to 20 months is so much more sensible than the few weeks so many previous studies have been based on.

T3-4-Hypo trial

Updated on 25 January 2024

CALL – study T3 / T4 combination therapy

In most patients, an too slow or unactive thyroid (hypothyroidism) can be well treated with thyroid hormone (levothyroxine). However, about 15% of patients keep several complaints, even though blood levels are normal. These complaints are especially fatigue, but also concentration and memory problems, depressive complaints and gastrointestinal, muscle and joint complaints, leading to a reduced quality of life.

The target

The aim of the study is to check whether adding the thyroid hormone T3 to the T4 (levothyroxine) therapy can reduce the symptoms of fatigue and any other complaints.

Registration for participation in the study can now take place in:

Erasmus MC in Rotterdam

Maasstad Hospital in Rotterdam

Rijnstate Hospital in Arnhem

Franciscus Gasthuis & Vlietland in Rotterdam and Schiedam

Van Weel-Bethesda Hospital in Dirksland

Admiraal de Ruyter Hospital in Goes

Amsterdam UMC, location AMC

UMC in Groningen

Radboudumc in Nijmegen

Albert Schweitzer Hospital Dordrecht

Maxima MC in Eindhoven and Veldhoven Nieuw

Zuyderland MC in Heerlen and Sittard-LedNieuw

UMC Utrecht New

On the study website you can see the hospitals that will connect in the course of 2024 (srolling)..

In addition, it is being investigated whether there are certain properties that determine whether or not someone responds to this therapy. So that in the future it may be better to predict who will or will not benefit from this T3 / T4 combination therapy.

For Thyroid Organization Netherlands (SON), the start of the T3 -4-Hypo trial, as the research is officially called, is an important moment. This study is at the top of our knowledge agenda. This is a list of desired studies compiled based on the wishes of thyroid patients themselves and in collaboration with researcher doctors. SON has worked enthusiastically on the preparation of this study and will also be closely involved in the coming years and pay attention to the progress and – ultimately – the results of the research.

For whom

Patients 18 years of age or older with hypothyroidism (low-fed thyroid gland), who have been treated with levothyroxine with normal blood levels for at least 3 months.

In addition, there must be serious fatigue complaints with a major negative impact on daily life during the last 6 months, possibly in combination with other complaints.

Hypothyroidism may not exist from birth/first years of life, or be caused by a pituitary disorder, thyroid surgery, treatment with radioactive iodine or medications.

There are more rules for participation. The study website T3-4-Hypo trial also contains further information for both patients and doctors. Based on that information, your doctor can estimate whether you are eligible for this examination.

Study design

A total of 600 patients will participate throughout the Netherlands. The examination takes 16 to 20 months for the patient and consists of two parts:

The transition to the same T4 drug (levothyroxine *) (part A)

The research comparing T4T4/T3 combination therapy with T4 /placebo therapy (part B).

There are two groups. In both groups, patients receive levothyroxinelevothyroxine*. However, one group is added T3 in addition to the levothyroxine. In addition to levothyroxine, the other group receives a placebo, a ‘nePMed icijn’. Both the doctor and the patient do not know who had what. This is the most reliable way to investigate the efficacy of treatment.

* Because 7 different T4 preparations are available in the Netherlands with different properties, it was decided to give all patients the same T4 medication first. This drug was developed specifically for this study. It is the only way to get reliable study results and make a comparison between T3T3/T4 combination therapy and T4 /placebo.

Participating hospitals

On the T3-4 Hypo trial website you will find an overview of participating hospitals ( scrolling down on the study website).

Do you want to participate in the research?

If you want to participate in the study, contact your treating doctor. You can bring this flyer (see picture). Your doctor can then read the information intended for doctors on the study website T3-4-Hypo trial to see if you are indeed eligible.

** Automatic ** translation from Dutch - lots of questionable results:

schildklier.nl/kennisbank/w...

[TiggerMe]

Fantastic!! 👏👏👏

[SarahJane1471]

🙋‍♀️please can I move and participate

[YorkshireLass_1964]

Fingers crossed for us all who need T3 and hopefully someone in UK research will take note 🤞🤞

[DippyDame]

t3-4-hypotrial.nl/english/

The stated aim of the study is...

To investigate whether addition of liothyronine (LT4/LT3 combination therapy) in patients with persistent tiredness on LT4 (levothyroxine) monotherapy is effective or not in relieving tiredness.

However, about 15% of patients keep several complaints, even though blood levels are normal

Patients 18 years of age or older with hypothyroidism (low-fed thyroid gland), who have been treated with levothyroxine with normal blood levels for at least 3 months.

I wonder how they define " normal"!

Being a natural cynic and someone who relies on a supraphysiological dose of T3 to function, as a consequence of having a form of Thyroid Hormone Resistance/ Impaired Sensitivity to Thyroid Hormone, I will be interested to discover how this pans out... given that each patient and their individual needs are very different

We already know that impaired T4 to T3 conversion is a major factor in determining a need for added T3. In addition to this we know that the T3 must reach the nuclei of the cells and attach to the T3 receptors to become active.

Crucially there are no tests to establish cellular level of T3, at least not on living tissue. This testing would in turn be well nigh impossible because different tissues in the body require different levels of T3 to achieve euthyroidism.

We already know that one role of thyroid hormones is to promote oxygen delivery to tissues. So, if you have low thyroid hormone levels (hypothyroidism), your tissues may have low oxygen levels....and fatigue is a result.

This study appears to overlook the fact that as human beings with a multitude of complexities we cannot be treated like machines that can be calibrated to a set point...in other words we cannot be medicated on the basis of a list of prescribed numbers.

We have already seen that with TSH testing....it doesn't work and more to the point insistance on it's value can leave patients very unwell.

Yet, it apppears that TSH level is an important starting point in this trial.....not thyroid hormone levels

This is because we want to ensure that we only enrol patients with a stable (i.e. normal) TSH on a stable dose of generic LT4, as recent dose adjustments could otherwise impact the tiredness questionnaire scores at the start of the tria

I would argue that we already have the tools to determine who needs T3 what we need is to have practitioners adequately qualified to analyse lab results and to understand how to medicate according to the patients symptoms and personal needs

This drug was developed specifically for this study. It is the only way to get reliable study results and make a comparison between T3T3/T4 combination therapy and T4 /placebo.

Strictly speaking "this drug" is a replacement T4 hormone. Do they intend to also develop a T3 replacement hormone specifically for the study?

I hope they can determine who needs T3, how much, and how it requires to be administered on an individual basis given the factors involved ....so that all existing symptoms are relieved

Although no detrimental effects of these low physiological LT3 dosages are expected

It appears they are to use only low T3 doses....but there is surely no guarantee that a low dose of T3 will be adequate to relieve the symptoms being investigated!

Right now, I'm not ready to remove my cynic's hat!!

Just my thoughts!

[helvella Administrator Thyroid UK in reply to DippyDame]

I would argue that we already have the tools to determine who needs T3 what we need is to have practitioners adequately qualified to analyse lab results and to understand how to medicate according to the patients symptoms and personal needs.

But we need the proof (as in accepted published paper(s)) in order for anyone to even accept they should be looking at whether anyone needs T3! Until we get over that fence, we get nowhere.

[DippyDame in reply to helvella]

I take your point and I hope that despite the many variables they can establish definitively that certain patients will require certain levels of T3.

But, I'm not convinced.

We have had papers declaring TSH as the gold standard test, that has been accepted as proof enough to have the result adhered to. It just created another hurdle.

Sorry, in haste, have to be at a appointment soon.

[Brightness14]

Looks to be a very interesting study for a good period of time. I wonder exactly what questions will be asked. A very complicated study but at least there are trying.

[helvella Administrator Thyroid UK in reply to Brightness14]

The less-than-perfect translation possibly makes it look more complicated.

[Brightness14]

Yes, maybe but at least they are trying to work it out, good luck to them. There are so many variables but it makes good sense to try something. Interesting to find what there come up with.

[helvella Administrator Thyroid UK in reply to Brightness14]

Shame that they have managed not to do such seemingly well-considered trials in the 65+ years since liothyronine (Tertroxin and Cytomel being the first branded products) became available.

[Just a general lament.]

[Brightness14]

Yes I have felt exactly the same as you, 65 years of suffering seems a tad to long.