From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history

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).[1] CT38 was developed as a synthetic analog of urocortin II by Cortene.[2]

Hypothesis[edit | edit source]

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,[1] it is also suggested that this will lead to an increase in serotonin expression.[2] 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.[3] 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.

Evidence[edit | edit source]

InTiME[edit | edit source]

Evidence is very limited, with only first clinical trial, an open-label phase 1/2 trial involving 14 ME/CFS patients published.[1] 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.[4]

Clinicians[edit | edit source]

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.[1]

Risks and safety[edit | edit source]

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. [4]

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. [5]

Costs and availability[edit | edit source]

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[edit | edit source]

Notable studies[edit | edit source]

  • 2021, Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome[6] (Full text)

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 1.2 1.3 Bateman, Lucinda. "Clinical Trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome". clinicaltrials.gov. Retrieved March 6, 2019.
  2. 2.0 2.1 2.2 Johnson, Cort (July 14, 2018). "The Cortene Chronic Fatigue Syndrome (ME/CFS) Drug Trial Begins". Health Rising. Retrieved March 6, 2019.
  3. Nelson, Maximillian J.; Bahl, Jasvir S.; Buckley, Jonathan D.; Thomson, Rebecca L.; Davison, Kade (October 2019). "Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and meta-analysis". Medicine. 98 (43): e17600. doi:10.1097/MD.0000000000017600. ISSN 0025-7974.
  4. 4.0 4.1 Bateman, Lucinda (December 7, 2018). "Pilot phase 1/2 Open-label, clinical trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (InTiME)" (PDF). Retrieved June 6, 2020.
  5. Tsuda, Takuma; Takefuji, Mikito; Wettschureck, Nina; Kotani, Kazuhiko; Morimoto, Ryota; Okumura, Takahiro; Kaur, Harmandeep; Eguchi, Shunsuke; Sakaguchi, Teruhiro (July 3, 2017). "Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction". Journal of Experimental Medicine. 214 (7): 1877–1888. doi:10.1084/jem.20161924. ISSN 0022-1007. PMC 5502432. PMID 28550160.
  6. Pereira, Gerard; Gillies, Hunter; Chanda, Sanjay; Corbett, Michael; Vernon, Suzanne D.; Milani, Tina; Bateman, Lucinda (2021). "Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Frontiers in Systems Neuroscience. 15: 84. doi:10.3389/fnsys.2021.698240. ISSN 1662-5137. PMC 8441022. PMID 34539356.