CT38

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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).[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 upregulation of CRF2, 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 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.[3] 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[edit | edit source]

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

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, the Fukuda criteria for chronic fatigue syndrome and the systemic exertion intolerance disease criteria.[1]Suzanne Vernon is the study director.[1]

Risks and safety[edit | edit source]

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. [4]

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. [5]

Costs and availability[edit | edit source]

Notable studies[edit | edit source]

Articles, talks and interviews[edit | edit source]

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. 1.01.11.21.31.4 Bateman, Lucinda. "Clinical Trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome". clinicaltrials.gov. Retrieved Mar 6, 2019. 
  2. 2.02.12.2 Johnson, Cort (Jul 14, 2018). "The Cortene Chronic Fatigue Syndrome (ME/CFS) Drug Trial Begins". Health Rising. Retrieved Mar 6, 2019. 
  3. Nelson, Maximillian J.; Bahl, Jasvir S.; Buckley, Jonathan D.; Thomson, Rebecca L.; Davison, Kade (Oct 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. Bateman, Lucinda (Dec 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 Jun 6, 2020. 
  5. Tsuda, Takuma; Takefuji, Mikito; Wettschureck, Nina; Kotani, Kazuhiko; Morimoto, Ryota; Okumura, Takahiro; Kaur, Harmandeep; Eguchi, Shunsuke; Sakaguchi, Teruhiro (Jul 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 5502432Freely accessible. PMID 28550160. 

ME/CFS - An acronym that combines myalgic encephalomyelitis with chronic fatigue syndrome. Sometimes they are combined because people have trouble distinguishing one from the other. Sometimes they are combined because people see them as synonyms of each other.

phase one - A drug trial involving only a small group of humans, often healthy volunteers, to assess drug safety and side effects. Typically 20-80 participants, often using a comparison group.

tachycardia - An unusually rapid heart beat. Can be caused by exercise or illness. A symptom of postural orthostatic tachycardia syndrome (POTS). (Learn more: www.heart.org)

The information provided at this site is not intended to diagnose or treat any illness.
From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history.