CT38

CT38 is an experimental peptide (i.e., two or more amino acids linked in a chain) that acts as an agonist for CRFR2 (corticotropin releasing factor receptor type 2). CT38 was developed as a synthetic analog of urocortin II by Cortene.

Hypothesis
The primary hypothesis for the use of CT38 is that symptoms arise due to the CRFR2 upregulation, leading to an oversensitive adrenocorticotropic hormone (ACTH) response to minor stimulation of the hypothalamus, it is also suggested that this will lead to an increase in serotonin expression. It is proposed that CT38 therapy will stimulate CRFR2, leading to a downregulation of receptor expression and thus normalisation of the response to corticotropin-releasing hormone (CRH) at the end of the therapy.

Hypothetically, CT38 may increase symptoms while the peptide is being taken, if this is a key mechanism involved in ME/CFS. In animal models, increased CRFR2 stimulation has been shown to lead to increased sympathetic nervous system activation. However, increased sympathetic nervous system activation is not consistently found in ME/CFS patients, with shifts in some patients to a sympathetic predominance instead explained by a reduction of parasympathetic nervous system activity. Currently, there is a lack of evidence for the dysregulation of CRFR2 expression in ME/CFS patients but if the trial is successful, this would increase research interest in this area.

InTiME
Evidence is very limited, with only first clinical trial, an open-label phase 1/2 trial involving 14 ME/CFS patients published. The trial was successful, although after CT38 was given to the first two ME/CFS patients, the dose needed to be lowered for remaining patients.

InTiME is the name of the initial CT38 trial.

Clinicians
Lucinda Bateman is the principal investigator for a current clinical trial of CT38 for ME/CFS, it is only being tested on patients who meet the Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome, the Fukuda criteria for chronic fatigue syndrome and the systemic exertion intolerance disease criteria. Suzanne Vernon is the study director.

Risks and safety
In healthy subjects, adverse effects Dr Lucinda Bateman reported (as part of the clinical trial protocol), were that escalating doses caused hypotension and tachycardia, with one subject reporting a heart rate of 160 BPM at a dose of 1.667 μg/kg. The expected maximum tolerable dose is expected to be to be 0.833 μg/kg, causing "mild" hypotension without signficant tachycardia.

Overall Safety in humans is currently unknown due to insufficient study, however Urocortin 2 stimulation of CRFR2 has been shown to cause cardiac dysfunction and can increase risk of heart failure in mice.

Costs and availability
CT38 is not yet approved for use, so it is unavailable outside clinical trials. CT38 is administered by subcutaneous infusion. Costs in future are unknown.

Articles, talks and interviews

 * 2018, The Cortene Chronic Fatigue Syndrome (ME/CFS) Drug Trial Begins

Notable studies

 * 2021, Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Full text)

Learn more

 * Clinical Trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
 * Hypothesis behind CT38 - Cortene
 * Sep 2021, Cortene Weighs-In on Future Plans for CT38 - Bateman Horne Center
 * Sep 2021, Cortene study published
 * Sep 2021, Dr Bateman on Cortene and CT38