Histaminergic Basis of Central Fatigue in Multiple Sclerosis - A Novel Approach

NCT03266965 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 20161186W81XWH-16-1-0462
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The histaminergic system is phylogenetically one of the oldest parts of the nervous system but it is a relatively recent discovery. It is involved with several vegetative functions like sleep, attention and learning, feeding and satiety, working memory, cognition, depression, and most of all arousal and energy

Conditions

Multiple Sclerosis

Keywords

Fatigue; Histamine

Outcome Measures

Primary Outcomes (1)

• Number of adverse events experienced by participants.

  All adverse and serious adverse events reported during the study will be analyzed and tabulated. No quantitative statistical analysis will be performed. The primary goal of this study is to establish that this intervention is safe and possibly effective.

  30 days

Secondary Outcomes (6)

• Change extent of fatigue.

  Screening(0 day), baseline(15 days) and final visit(30 days)

• Change in Quality of life.

  Screening(0 day), baseline(15 days) and final visit(30 days)

• Change of fatigue impact scale.

  Screening(0 day), baseline(15 days) and final visit(30 days)

• Change of visual pain.

  Screening(0 day), baseline(15 days) and final visit(30 days)

• Change of daytime sleepiness.

  Screening(0 day), baseline(15 days) and final visit(30 days)

Study Arms (1)

Histidine Intervention Group

EXPERIMENTAL

A total of 15 subjects will be recruited in batches of 5 until completed 15 subjects in the trial. If a subject withdraws the trial, the study will continue and enrolling subjects until 15 of them complete the trial. The subject composition (MS patient/Normal subject) 4 MS and 1 normal will be tested on a dose of L-Histidine 250 mg plus Lodosyn 50 mg BID for seven days. If there are no safety concerns, the next 5 patients will be recruited 4 MS and 1 normal to test the dose of 500 mg with Lodosyn 50 mg bid for seven days. If there are no safety concerns, then L-histidine 1,000 mg plus Lodosyn (Carbidopa) 50 mg bid will be tested in the next 5 subjects 4 MS and 1 normal for seven days.

Drug: Carbidopa; Dietary Supplement: L-Histidine

Interventions

Carbidopa DRUG

All subjects will receive a fixed dose of 50mg of Lodosyn twice daily.

Also known as: Lodosyn

Histidine Intervention Group

L-Histidine DIETARY_SUPPLEMENT

Sequential Dose Escalation of 250mg to 500mg to 1000mg twice daily.

Histidine Intervention Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects between the ages of 18 and 60 will be eligible.
• Subjects should be in good physical health without history of chronic illness and should be generally considered healthy.
• Spouses or caregivers of patients with MS would be encouraged to participate.
• Patients with MS regardless of the disease type, who experience severe fatigue will be eligible to participate.

You may not qualify if:

• Established MS by McDonald Criteria - 2010 Revision (24). Relapse Remitting (RR) 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 Therapy (DMT)
• Adults unable to give informed consent due to cognitive impairment or mental disorders.
• Children below the age of consent
• Pregnant women
• Prisoners
• History of chronic disorders like hypertension, diabetes, hyperlipidemia, depression, hypothyroidism etc. that require chronic treatment
• 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
• Adults unable to give informed consent due to cognitive impairment or mental disorders.

Sponsors & Collaborators

• University of Miami: lead
• United States Department of Defense: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis; Fatigue

Interventions

Carbidopa; Histidine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methyldopa; Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Hydrazines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Kottil Rammohan, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Of Clinical Neurology

Study Record Dates

• First Submitted: July 4, 2017
• First Posted: August 30, 2017
• Study Start: March 23, 2018
• Primary Completion: August 7, 2020
• Study Completion: August 7, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)