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Clinical Trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (InTiME)

Primary Purpose

Myalgic Encephalomyelitis, Chronic Fatigue Syndrome

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CT38
Sponsored by
LUCINDA BATEMAN, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myalgic Encephalomyelitis focused on measuring myalgic encephalomyelitis, chronic fatigue syndrome, corticotropin releasing-factor receptor subtype 2 (CRF2), Alternative CRF2 names: CRFR2, CRH2, CRHR2

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provision of signed and dated informed consent form
  • Ability to read, understand and speak English
  • Living at an altitude between 3,500 and 5,500 feet above sea level for the past 1 year
  • Willing to perform an exercise test
  • Diagnosed with ME/CFS and meet the following 3 case definitions: Fukuda Research Case Definition for CFS (1994), Revised Canadian Consensus Criteria for ME/CFS (2010) and the Institute of Medicine (IOM) Clinical Diagnostic Criteria for ME/CFS (2015)
  • Relatively stable state of illness for the individual patient over the past 3 months
  • Male or female, between the ages of 18 and 60 years old
  • Males or females of reproductive potential agree to remain abstinent or use (or have their partner use) 2 acceptable methods of contraception, starting from the time of informed consent through 28 days after the last dose of study drug. Acceptable methods of birth control during the study are intrauterine device, diaphragm with spermicide, contraceptive sponge, condom or vasectomy. Oral contraceptive pills may not be used as the sole method of contraception because the effect of CT38 on the efficacy of oral contraceptive pills has not yet been established
  • Stated willingness to comply with all study procedures and remain available for the study duration
  • Have mobile (smart) phone and access to the internet

Exclusion Criteria:

  • Alternate medical or psychiatric illness that could explain the ME/CFS symptoms
  • Unwilling or unable to perform an exercise test
  • Active or uncontrolled co-morbidities which in the opinion of the PI may interfere with the ability of the patient to participate in the study. Co-morbidities may include acute infection, Crohn's disease, diabetes mellitus (Type 1 or Type 2, evidenced by a history of glycated hemoglobin (A1C) > 7 at any time), Guillain-Barre syndrome, lupus, multiple sclerosis, myasthenia gravis, rheumatoid arthritis, or other such diseases that may be exclusionary. Particularly conditions or medications that cause immunodeficiency or immunosuppression will be excluded. Examples of such conditions can be found in the tables "Causes of Secondary Immunodeficiency" and "Some Drugs that Cause Immunosuppression" in the "Merck Manual"
  • Pregnancy, or while breast feeding. Women should not be enrolled within 6 months of giving birth and within 3 months of cessation of breast feeding
  • A Body Mass Index > 35
  • Cigarette smoker or former smoker who has smoked within 6 months of the start of the study
  • Living at an altitude that is more than 1,000 feet (lower or higher) from the study site (which is 4,500 feet above sea level)
  • History of:

    • Major depression with psychotic or melancholic features before the diagnosis of ME/CFS, or active depression (major depression with psychotic or melancholic features) as determined by self-report
    • Untreated endocrine diagnoses including hypothyroidism (Hashimoto's, etc.), Grave's disease, adrenal insufficiency, hypogonadism (testosterone deficiency), diabetes mellitus or insipidus
    • Acute infection within the past 30 days
    • Within the last 3 years, any significant head injury, e.g., concussion with loss of consciousness, brain surgery, an automobile accident with head/neck injury, other traumatic brain injury
    • A supra-ventricular tachycardia or ventricular tachycardia, e.g., atrial fibrillation or flutter, paroxysmal atrial fibrillation, junctional tachycardia, ventricular tachycardia
    • Severe baseline hypotension defined as rested sitting systolic BP < 100 mmHg or rested sitting diastolic BP < 60 mmHg
    • Renal impairment based upon the local lab normal estimated glomerular filtration rate (eGFR) (drug is cleared by passive renal filtration)
    • Known hypersensitivity or clinically significant allergies to tromethamine or Tween 80 (both excipients in the drug product)
    • Substance abuse in the past 12 months as determined by self-report
  • Improvement in overall ME/CFS symptoms as a result of any treatment intervention in the past 3 months
  • Current treatment with medications that interact with pathways involving: (i) 5-hydroxytryptamine (5HT) (e.g., selective 5HT re-uptake inhibitors or selective serotonin reuptake inhibitors (SSRIs), 5HT and norepinephrine re-uptake inhibitors or serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors, triptans); (ii) norepinephrine (e.g., adrenergic agonists or antagonists, norepinephrine re-uptake inhibitors, norepinephrine and dopamine re- uptake inhibitors); (iii) dopamine (e.g., norepinephrine and dopamine re-uptake inhibitors); and (iv) cortisol pathways (e.g., oral glucocorticoids, fludrocortisone).
  • Prior treatment with

    • Short-term (< 2 weeks) antiviral or antibiotic medication or flu shot within the past 4 weeks
    • Long-term (> 2 weeks) antiretrovirals within the past 12 months
    • RituximabTM within 6 months
    • Any new prescription drug or herbal remedy within 2 weeks prior to the onset of the trial
  • Current participation in another clinical treatment trial

Sites / Locations

  • Bateman Horne Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

D0.20

D0.03

D0.06

D0.01

Arm Description

Subcutaneous infusion of CT38 at 0.20 μg/kg/hour, for 3 hours on each of 2 days

Subcutaneous infusion of CT38 at 0.03 μg/kg/hour, for 3.5 hours on each of 3 days

Subcutaneous infusion of CT38 at 0.06 μg/kg/hour, for 3.5 hours on each of 3 days

Subcutaneous infusion of CT38 at 0.01 μg/kg/hour, for 3.5 hours on each of 3 days

Outcomes

Primary Outcome Measures

Total Daily Symptom Score (TDSS)
Pre-/post-treatment difference in TDSS (0-65 scale, 0=no symptoms; 65=maximum of 5 for each of 13 specific patient-reported symptoms). The TDSS sums the patient-reported daily symptom score for each of 13 specific symptoms (including fatigue, muscle/joint pain, sleep problems, cognitive problems, orthostatic intolerance, body temperature perceptions, flu-like symptoms, headaches or sensitivities, shortness of breath, gastrointestinal problems, urogenital problems, anxiety and depression), each assessed on a 0-5 scale (0=no symptom, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=severe)

Secondary Outcome Measures

SF-36, PCS
Pre-/post-treatment difference in the physical component score (PCS) of the RAND 36-Item Health Survey (SF-36), on a 0-100 scale (where 0=max disability and 100=no disability)
SF-36, MCS
Pre-/post-treatment difference in the mental component score (MCS) of the RAND 36-Item Health Survey (SF-36), on a 0-100 scale (where 0=max disability and 100=no disability)

Full Information

First Posted
July 13, 2018
Last Updated
April 30, 2020
Sponsor
LUCINDA BATEMAN, MD
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1. Study Identification

Unique Protocol Identification Number
NCT03613129
Brief Title
Clinical Trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
Acronym
InTiME
Official Title
Pilot Phase 1/2, Open-Label, Clinical Trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
July 23, 2018 (Actual)
Primary Completion Date
April 30, 2019 (Actual)
Study Completion Date
April 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
LUCINDA BATEMAN, MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study seeks to investigate the safety, tolerability and efficacy of CT38, an experimental peptide administered by subcutaneous infusion, in the treatment of ME/CFS patients.
Detailed Description
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is a complex disorder that may be triggered by infection or other stressors (e.g., emotional or physical trauma, immune activation, chemical exposures). Its hallmark is a reduced capacity for physical and mental activity manifest as profound fatigue along with a cascade of debilitating symptoms (including pain, cognitive dysfunction, orthostatic intolerance, sensitivities, and irregularities of the autonomic, immune and metabolic systems) that worsen with activity (referred to as post-exertional malaise or PEM), are not improved by sleep, and can persist for years. Patients are often unable to handle the activities of daily living and experience a loss of career and a very poor quality of life. There are no established diagnostic tests or approved therapeutics for ME/CFS. The cause of ME/CFS is not known. It has been postulated that ME/CFS could arise from the up-regulation of a specific receptor (CRF2) in those parts of the brain that govern the sensitivity of the stress response. This configuration would invoke a major response to a minor stimulus, ultimately leading to neuroendocrine, autonomic, immune and metabolic abnormalities that are commonly observed. There is no animal model of ME/CFS, but overstimulating CRF2 in healthy rats, induces signs and symptoms consistent with the disease in humans; while down-regulating it, via CT38 (an experimental peptide), eliminates the ability to stimulate these signs and symptoms. Hypothesis: Utilize CT38 to down-regulate CRF2 to restore a normal stress response, and potentially eliminate disease signs and symptoms. The study will enroll 18 patients, who meet the Fukuda and Canadian criteria for ME/CFS, and treat them with various doses of CT38. The primary endpoint will be the change in the average total daily symptom score (TDSS), over 28-day periods immediately prior to the first treatment (pre-treatment) and immediately prior to exit from the trial (post-treatment). The TDSS is the sum of 13 individual symptom scores, each recorded daily by the patient on a 6-point scale (0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=very severe). The individual symptoms included fatigue, muscle/joint pain, sleep issues (e.g., un-refreshing sleep, difficulty falling or staying asleep, excessive sleepiness), cognitive issues (e.g., slow information processing, memory difficulties, inability to concentrate/focus, attention deficit), orthostatic intolerance (e.g., dizziness, spatial disorientation, light-headedness, feeling faint), body temperature perceptions, flu-like symptoms (e.g., sore throat, tender lymph nodes, swollen glands, fever, chills, sinus/nasal problems), headaches or sensory sensitivities (to light, sound, smell, touch, taste), shortness of breath, gastrointestinal problems (e.g., nausea, stomach/abdominal pain, diarrhea), urogenital problems (e.g., frequent urination), anxiety and depression. The secondary outcomes will assess general health status (determined by Short-Form 36, or SF-36), as well as safety assessments.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myalgic Encephalomyelitis, Chronic Fatigue Syndrome
Keywords
myalgic encephalomyelitis, chronic fatigue syndrome, corticotropin releasing-factor receptor subtype 2 (CRF2), Alternative CRF2 names: CRFR2, CRH2, CRHR2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
The study is comprised of a recruitment and screening period, enrollment (Visit 1), a 4-week (at least) pre-treatment assessment period, a 1-week interventional treatment period with drug infused at Visits 3, 4 and 4b, a 4-week (at least) post-treatment assessment period, and a close-out (Visit 6).
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
D0.20
Arm Type
Active Comparator
Arm Description
Subcutaneous infusion of CT38 at 0.20 μg/kg/hour, for 3 hours on each of 2 days
Arm Title
D0.03
Arm Type
Active Comparator
Arm Description
Subcutaneous infusion of CT38 at 0.03 μg/kg/hour, for 3.5 hours on each of 3 days
Arm Title
D0.06
Arm Type
Active Comparator
Arm Description
Subcutaneous infusion of CT38 at 0.06 μg/kg/hour, for 3.5 hours on each of 3 days
Arm Title
D0.01
Arm Type
Active Comparator
Arm Description
Subcutaneous infusion of CT38 at 0.01 μg/kg/hour, for 3.5 hours on each of 3 days
Intervention Type
Drug
Intervention Name(s)
CT38
Intervention Description
Infusion
Primary Outcome Measure Information:
Title
Total Daily Symptom Score (TDSS)
Description
Pre-/post-treatment difference in TDSS (0-65 scale, 0=no symptoms; 65=maximum of 5 for each of 13 specific patient-reported symptoms). The TDSS sums the patient-reported daily symptom score for each of 13 specific symptoms (including fatigue, muscle/joint pain, sleep problems, cognitive problems, orthostatic intolerance, body temperature perceptions, flu-like symptoms, headaches or sensitivities, shortness of breath, gastrointestinal problems, urogenital problems, anxiety and depression), each assessed on a 0-5 scale (0=no symptom, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=severe)
Time Frame
28 days preceding Visit 3 (pre-treatment) and 28 days preceding Visit 6 (post-treatment)
Secondary Outcome Measure Information:
Title
SF-36, PCS
Description
Pre-/post-treatment difference in the physical component score (PCS) of the RAND 36-Item Health Survey (SF-36), on a 0-100 scale (where 0=max disability and 100=no disability)
Time Frame
Visit 3 before treatment (pre-treatment) and at Visit 6 (post-treatment)
Title
SF-36, MCS
Description
Pre-/post-treatment difference in the mental component score (MCS) of the RAND 36-Item Health Survey (SF-36), on a 0-100 scale (where 0=max disability and 100=no disability)
Time Frame
Visit 3 before treatment (pre-treatment) and at Visit 6 (post-treatment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of signed and dated informed consent form Ability to read, understand and speak English Living at an altitude between 3,500 and 5,500 feet above sea level for the past 1 year Willing to perform an exercise test Diagnosed with ME/CFS and meet the following 3 case definitions: Fukuda Research Case Definition for CFS (1994), Revised Canadian Consensus Criteria for ME/CFS (2010) and the Institute of Medicine (IOM) Clinical Diagnostic Criteria for ME/CFS (2015) Relatively stable state of illness for the individual patient over the past 3 months Male or female, between the ages of 18 and 60 years old Males or females of reproductive potential agree to remain abstinent or use (or have their partner use) 2 acceptable methods of contraception, starting from the time of informed consent through 28 days after the last dose of study drug. Acceptable methods of birth control during the study are intrauterine device, diaphragm with spermicide, contraceptive sponge, condom or vasectomy. Oral contraceptive pills may not be used as the sole method of contraception because the effect of CT38 on the efficacy of oral contraceptive pills has not yet been established Stated willingness to comply with all study procedures and remain available for the study duration Have mobile (smart) phone and access to the internet Exclusion Criteria: Alternate medical or psychiatric illness that could explain the ME/CFS symptoms Unwilling or unable to perform an exercise test Active or uncontrolled co-morbidities which in the opinion of the PI may interfere with the ability of the patient to participate in the study. Co-morbidities may include acute infection, Crohn's disease, diabetes mellitus (Type 1 or Type 2, evidenced by a history of glycated hemoglobin (A1C) > 7 at any time), Guillain-Barre syndrome, lupus, multiple sclerosis, myasthenia gravis, rheumatoid arthritis, or other such diseases that may be exclusionary. Particularly conditions or medications that cause immunodeficiency or immunosuppression will be excluded. Examples of such conditions can be found in the tables "Causes of Secondary Immunodeficiency" and "Some Drugs that Cause Immunosuppression" in the "Merck Manual" Pregnancy, or while breast feeding. Women should not be enrolled within 6 months of giving birth and within 3 months of cessation of breast feeding A Body Mass Index > 35 Cigarette smoker or former smoker who has smoked within 6 months of the start of the study Living at an altitude that is more than 1,000 feet (lower or higher) from the study site (which is 4,500 feet above sea level) History of: Major depression with psychotic or melancholic features before the diagnosis of ME/CFS, or active depression (major depression with psychotic or melancholic features) as determined by self-report Untreated endocrine diagnoses including hypothyroidism (Hashimoto's, etc.), Grave's disease, adrenal insufficiency, hypogonadism (testosterone deficiency), diabetes mellitus or insipidus Acute infection within the past 30 days Within the last 3 years, any significant head injury, e.g., concussion with loss of consciousness, brain surgery, an automobile accident with head/neck injury, other traumatic brain injury A supra-ventricular tachycardia or ventricular tachycardia, e.g., atrial fibrillation or flutter, paroxysmal atrial fibrillation, junctional tachycardia, ventricular tachycardia Severe baseline hypotension defined as rested sitting systolic BP < 100 mmHg or rested sitting diastolic BP < 60 mmHg Renal impairment based upon the local lab normal estimated glomerular filtration rate (eGFR) (drug is cleared by passive renal filtration) Known hypersensitivity or clinically significant allergies to tromethamine or Tween 80 (both excipients in the drug product) Substance abuse in the past 12 months as determined by self-report Improvement in overall ME/CFS symptoms as a result of any treatment intervention in the past 3 months Current treatment with medications that interact with pathways involving: (i) 5-hydroxytryptamine (5HT) (e.g., selective 5HT re-uptake inhibitors or selective serotonin reuptake inhibitors (SSRIs), 5HT and norepinephrine re-uptake inhibitors or serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors, triptans); (ii) norepinephrine (e.g., adrenergic agonists or antagonists, norepinephrine re-uptake inhibitors, norepinephrine and dopamine re- uptake inhibitors); (iii) dopamine (e.g., norepinephrine and dopamine re-uptake inhibitors); and (iv) cortisol pathways (e.g., oral glucocorticoids, fludrocortisone). Prior treatment with Short-term (< 2 weeks) antiviral or antibiotic medication or flu shot within the past 4 weeks Long-term (> 2 weeks) antiretrovirals within the past 12 months RituximabTM within 6 months Any new prescription drug or herbal remedy within 2 weeks prior to the onset of the trial Current participation in another clinical treatment trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lucinda Bateman, MD
Organizational Affiliation
Bateman Horne Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Suzanne D Vernon, PhD
Organizational Affiliation
Bateman Horne Center
Official's Role
Study Director
Facility Information:
Facility Name
Bateman Horne Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84102
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34539356
Citation
Pereira G, Gillies H, Chanda S, Corbett M, Vernon SD, Milani T, Bateman L. Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Syst Neurosci. 2021 Sep 1;15:698240. doi: 10.3389/fnsys.2021.698240. eCollection 2021.
Results Reference
derived

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Clinical Trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome

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