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

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ClinicalTrials.gov Identifier: NCT03613129
Recruitment Status : Recruiting
First Posted : August 2, 2018
Last Update Posted : August 2, 2018
Sponsor:
Information provided by (Responsible Party):
LUCINDA BATEMAN, MD, Bateman Horne Center

Brief Summary:
This study seeks to examine the effect of a subcutaneous infusion of CT38, an experimental peptide, on cardio-pulmonary exercise test (CPET) performance and CPET-induced changes in functional capacity and symptom levels (assessed by, Fitbit monitoring, DANA cognitive testing and patient-reported outcome measures) in ME/CFS.

Condition or disease Intervention/treatment Phase
Myalgic Encephalomyelitis Chronic Fatigue Syndrome Drug: CT38 Phase 1 Phase 2

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 induces, in healthy rats, 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 CDC, Fukuda and Canadian criteria for ME/CFS, and treat them with a low, intermediate or high dose of CT38.

The primary outcome will be an assessment of functional parameters following cardio-pulmonary exercise tests (CPET), conducted pre- and post-treatment.

The secondary outcomes will assess function, symptom exacerbation and recovery following CPET, assessed by, Fitbit monitoring, DANA cognitive testing, patient-reported outcome measures, effects on vitals, orthostatic intolerance and general health status, as well as safety assessments.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The study consists of a 2-week lead-in period, a first cardio-pulmonary exercise test (CPET1), a 4-week recovery period (following CPET1), a 2-week treatment period (during which drug will be administered by subcutaneous infusion on 2 separate days), a second CPET (CPET2), and a 4-week recovery period (following CPET2), followed by study exit. The study will test 3 dose-levels of the experimental drug CT38 (i.e., Low, Intermediate and High)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Phase 1/2, Open-Label, Clinical Trial to Investigate CT38 in the Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
Actual Study Start Date : July 23, 2018
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Low Dose CT38
A low dose of CT38 will be subcutaneously infused for 3 hours over each of 2 days
Drug: CT38
Sequentially ascending dose of CT38

Active Comparator: Intermediate Dose CT38
An intermediate dose of CT38 will be subcutaneously infused for 3 hours over each of 2 days
Drug: CT38
Sequentially ascending dose of CT38

Active Comparator: High Dose CT38
A high dose of CT38 will be subcutaneously infused for 3 hours over each of 2 days
Drug: CT38
Sequentially ascending dose of CT38




Primary Outcome Measures :
  1. Oxygen consumption (VO2) at ventilatory threshold, in ml/kg/min [ Time Frame: Day 15 (pre-treatment) and Day 57 (post-treatment) ]
    Pre-/post-treatment difference in oxygen consumption at ventilatory threshold, during CPET

  2. Work load at ventilatory threshold, in W [ Time Frame: Day 15 (pre-treatment) and Day 57 (post-treatment) ]
    Pre-/post-treatment difference in work load at ventilatory threshold, during CPET

  3. Oxygen consumption (VO2) at peak performance, in ml/kg/min [ Time Frame: Day 15 (pre-treatment) and Day 57 (post-treatment) ]
    Pre-/post-treatment difference in oxygen consumption at peak performance, during CPET

  4. Work load at peak performance, in W [ Time Frame: Day 15 (pre-treatment) and Day 57 (post-treatment) ]
    Pre-/post-treatment difference in work load at peak performance, during CPET


Secondary Outcome Measures :
  1. Activity level during recovery [ Time Frame: Days 16-42 (pre-treatment) and Days 58-84 (post-treatment) ]
    Pre-/post-treatment difference in CPET-exacerbated, Fitbit assessed activity levels, measured in calories (monitored continuously and summarized daily)

  2. Sleep quality during recovery [ Time Frame: Days 16-42 (pre-treatment) and Days 58-84 (post-treatment) ]
    Pre-/post-treatment difference in CPET-exacerbated, Fitbit assessed sleep quality, measured in hours spent in light sleep, REM sleep, deep sleep, or awake (monitored continuously and summarized daily)

  3. Cognitive function during recovery [ Time Frame: Days 16-42 (pre-treatment) and Days 58-84 (post-treatment) ]
    Pre-/post-treatment difference in CPET-exacerbated, DANA mobile assessed cognitive function (monitored daily)

  4. Symptoms during recovery [ Time Frame: Days 16-42 (pre-treatment) and Days 58-84 (post-treatment) ]
    Pre-/post-treatment difference in CPET-exacerbated, patient-reported symptom levels for each of 13 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), assessed daily on a 0-5 scale (0=no symptom, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=severe)

  5. Effect on orthostatic intolerance [ Time Frame: Days 1 (pre-treatment), 45 (post-treatment) and 85 (exit) ]
    Pre-/post-treatment difference in change in heart rate, when going from a supine to standing position

  6. Effect on heart rate [ Time Frame: Days 1 and 15 (pre-treatment), and Days 57 and 85 (post-treatment) ]
    Pre-/post-treatment difference in heart rate

  7. Effect on systolic and diastolic blood pressure [ Time Frame: Days 1 and 15 (pre-treatment), and Days 57 and 85 (post-treatment) ]
    Pre-/post-treatment difference in systolic and diastolic blood pressure

  8. Effect on general health status [ Time Frame: Days 43 (pre-treatment) and 85 (post-treatment) ]
    Pre-/post-treatment difference in general health status, assessed via RAND 36-Item Health Survey



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 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) 5HT (e.g., selective 5HT re-uptake inhibitors or SSRIs, 5HT and norepinephrine re-uptake inhibitors or 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03613129


Contacts
Contact: Lucinda Bateman, MD (801) 532-8311 LBateman@batemanhornecenter.org
Contact: Suzanne D Vernon, PhD (801) 532-8311 sdvernon@batemanhornecenter.org

Locations
United States, Utah
Bateman Horne Center Recruiting
Salt Lake City, Utah, United States, 84102
Contact: Lucinda Bateman, MD    801-359-7400    lbateman@batemanhornecenter.org   
Contact: Suzanne D Vernon, PhD    (801) 359-7400    sdvernon@batemanhornecenter.org   
Sponsors and Collaborators
LUCINDA BATEMAN, MD
Investigators
Principal Investigator: Lucinda Bateman, MD Bateman Horne Center
Study Director: Suzanne D Vernon, PhD Bateman Horne Center

Responsible Party: LUCINDA BATEMAN, MD, Founder & Medical Director, Bateman Horne Center
ClinicalTrials.gov Identifier: NCT03613129     History of Changes
Other Study ID Numbers: ME-101p
First Posted: August 2, 2018    Key Record Dates
Last Update Posted: August 2, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by LUCINDA BATEMAN, MD, Bateman Horne Center:
myalgic encephalomyelitis
chronic fatigue syndrome
corticotropin releasing-factor receptor subtype 2 (CRF2)
corticotropin releasing-hormone receptor subtype 2 (CRH2)

Additional relevant MeSH terms:
Syndrome
Fatigue
Fatigue Syndrome, Chronic
Encephalomyelitis
Myalgia
Disease
Pathologic Processes
Signs and Symptoms
Virus Diseases
Muscular Diseases
Musculoskeletal Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuromuscular Diseases
Central Nervous System Infections
Musculoskeletal Pain
Pain
Neurologic Manifestations
Corticotropin-Releasing Hormone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs