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Histaminergic Basis of Fatigue in Multiple Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04764383
Recruitment Status : Withdrawn (Withdrawn as more data drug analysis is recommended before the study.)
First Posted : February 21, 2021
Last Update Posted : July 29, 2021
Sponsor:
Information provided by (Responsible Party):
Kottil W. Rammohan, University of Miami

Study Description
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Brief Summary:
The purpose of this research study is to identify a way to improve the feeling of exhaustion that patients might experience because of Multiple Sclerosis (MS).

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: L-Histidine Drug: Placebo Drug: Lodosyn Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: double-blind randomized cross-over
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Histaminergic Basis of Fatigue in Multiple Sclerosis
Estimated Study Start Date : January 1, 2022
Estimated Primary Completion Date : October 30, 2022
Estimated Study Completion Date : October 30, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: PK/PD Group
Participants in the Pharmacokinetic (PK)/pharmacodynamic (PD) Group will receive L-Histidine and Lodosyn daily for 7 consecutive days.
 Drug: L-Histidine
1000 mg capsules taken by mouth (PO) twice daily (BID).
Other Name: Histamine

Drug: Lodosyn
50 mg capsules taken PO BID.
Placebo Comparator: L-Histidine and Lodosyn followed by Placebo Group
Participants in this group will receive L-Histidine and Lodosyn daily for 2 consecutive weeks followed by Placebo for an additional 2 consecutive weeks with a 1-week wash-out period in between.
 Drug: L-Histidine
1000 mg capsules taken by mouth (PO) twice daily (BID).
Other Name: Histamine

Drug: Placebo
Microcrystalline cellulose (placebo) 1000 mg capsules taken by mouth (PO) twice daily (BID).

Drug: Lodosyn
50 mg capsules taken PO BID.
Experimental: Placebo followed by L-Histidine and Lodosyn Group
Participants in this group will receive Placebo daily for 2 consecutive weeks followed by L-Histidine and Lodosyn for an additional 2 consecutive weeks with a 1 week wash out period in between.
 Drug: L-Histidine
1000 mg capsules taken by mouth (PO) twice daily (BID).
Other Name: Histamine

Drug: Placebo
Microcrystalline cellulose (placebo) 1000 mg capsules taken by mouth (PO) twice daily (BID).

Drug: Lodosyn
50 mg capsules taken PO BID.


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of Adverse Events [ Time Frame: Up to 5 weeks ]
    Adverse events will be evaluated by treating physician.


Secondary Outcome Measures :
  1. Efficacy as measured by FSS scores [ Time Frame: Up to 5 weeks ]
    Efficacy will be reported as the number of participants that dropped one point or more from their baseline Fatigue Severity Scale (FSS) scores. FSS is a 9-item questionnaire with questions related to how fatigue interferes with certain activities according to a self-reported scale. Each of the items are scored on a 7 point scale with 1 = strongly disagree and 7 = strongly agree.

  2. Efficacy as measured by MFIS Scores [ Time Frame: Up to 5 weeks ]
    Modified Fatigue Impact Scale (MFIS) is a scale is used to measure fatigue with the total score ranging from 0 to 84 with 0 being the best possible score and 84 being the worst score.

  3. Efficacy as measured by the VAS scores [ Time Frame: Up to 5 weeks ]
    The Visual Analog Scale (VAS) allows participants to rate their health on a 20 cm vertical with a higher number indicating better outcomes.

  4. Efficacy as measured by the MSQOL Scores [ Time Frame: Up to 5 weeks ]
    Multiple Sclerosis Quality of Life (MSQOL) has a total score ranging from 0 to 100 with a higher score indicating a better quality of life.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion and Exclusion Criteria

For Healthy (Normal) Participants

Inclusion Criteria:

  • Male or female subjects between the ages of 18 and 60
  • In good physical health without a history of chronic illness and considered generally healthy.

Exclusion Criteria:

  • Adults unable to give informed consent due to cognitive impairment or mental disorders.
  • Children below the age of consent
  • Pregnant women (if the pregnancy test is positive during any stage of the study, subject will be removed from it)
  • Prisoners
  • Chronic untreated disorders like hypertension, diabetes, hyperlipidemia, depression, hypothyroidism etc., that could confound or interfere with the proposed therapy in the view of the PI are excluded. Stable treated above conditions are not exclusionary.
  • Known chronic fatigue syndrome
  • Blood disorders or coagulopathy
  • Chronic allergies or history of asthma.
  • Using antihistamines, bronchodilators or H2 blockers for hyperacidity
  • Using medications for sleep, or known sleep disorders
  • Any medication or condition deemed unsuitable by the PI. If necessary, subjects should wash out such medications for a duration of at least 5 half-lives.
  • All medications prescribed and over the counter, should be approved by the PI during the duration of the trial.

For Multiple Sclerosis Participants

Inclusion Criteria:

  • Established Multiple Sclerosis by McDonald Criteria - 2010 Revision or McDonald Criteria 2017. Relapsing-Remitting and progressive forms of MS are eligible
  • Severe fatigue that has lasted greater than 6 months
  • Clinically stable on a current therapy with any Disease Modifying Therapies (DMT)
  • Fatigue Severity Score of >/= 4.0 will qualify as long as all other inclusion/exclusion criteria is met.

Exclusion Criteria:

  • Adults unable to give informed consent due to cognitive impairment or mental disorders.
  • Children below the age of consent
  • Pregnant women (if the pregnancy test is positive during any stage of the study, subject will be removed from it)
  • Prisoners
  • Systemic disorders known to cause fatigue such as severe anemia, infections, chronic systemic infectious or inflammatory disorders, including known autoimmune disorders. (allowed as long is not present. Subject might qualify as per discretion of the Principal Investigator)
  • Chronic fatigue syndrome
  • Hypothyroidism (If treated and/or controlled subject might qualify as per discretion of the Principal Investigator)
  • Systemic malignancy. Remote history of a malignancy is not a contraindication.
  • Undergoing chemotherapy
  • Depression (If treated and/or controlled subject might qualify as per discretion of the Principal Investigator)
  • Sleep disorders including narcolepsy, excessive day-time sleep. (If treated and/or controlled subject might qualify as per discretion of the Principal Investigator)
  • Ongoing substance abuse
  • Excessive consumption of coffee or over-the-counter stimulants. Use of caffeine is not exclusionary but subjects are instructed to not change the use for the duration of the study.
  • Concomitant medications of amantadine, methylphenidate, amphetamines, pemoline, barbiturates, tizanidine, MonoAmine Oxidase (MAO) inhibitors, benzodiazepines, barbiturates, tricyclic antidepressants, antihistamines, H2 blockers for Gastroesophageal reflux disease (GERD), Selective Serotonin Reuptake Inhibitor (SSRIs) and any other medication that in the opinion of the PI should be excluded. If used and approved by the PI at study entry, any change for the duration of the study is not permitted.
  • Patients who were using modafinil for treatment of fatigues prior to the study may participate but will be required to undergo a washout of five half-lives prior to entry into the trial.
Contacts and Locations
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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): NCT04764383


Locations
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United States, Florida
University of Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Investigators
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Principal Investigator: Kottil Rammohan, MD University of Miami
More Information
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Responsible Party: Kottil W. Rammohan, Professor of Clinical Neurology, University of Miami
ClinicalTrials.gov Identifier: NCT04764383    
Other Study ID Numbers: 20201550
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: July 29, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Kottil W. Rammohan, University of Miami:
Fatigue
Histamine
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Fatigue
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
 Autoimmune Diseases
Immune System Diseases
Histamine
Histamine Agonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs