CT38

CT38 is an experimental peptide (i.e., two or more amino acids linked in a chain) that acts as an agonist for CRF2 (corticotropin-releasing factor 2 receptor). 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 upregulation of CRF2, 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 CRF2, leading to a downregulation of receptor expression and thus normalisation of the response to Corticotropin-releasing hormone (CRH) upon cessation 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 CRF2 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 CRF2 expression in ME/CFS patients but if the trial is successful, this would increase research interest in this area.

Evidence
Evidence is not yet available, with results of the Phase 1/2, Open-Label trial not yet published.

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, 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 Lucinda Bateman reported (as part of the clinical trial protocol), that escalating doses cause 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 CRF2 has been shown to cause cardiac dysfunction and can increase risk of heart failure in mice.

Articles, talks and interviews

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

Learn more

 * Clinical Trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
 * Science - Hypothesis behind CT38