Histaminergic Basis of Central Fatigue in Multiple Sclerosis - A Novel Approach - Clinical Trial for Multiple Sclerosis | NCT03266965

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Carbidopa

L-Histidine

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Fatigue, Histamine

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for Healthy Volunteers:

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.

Inclusion Criteria for Patients with Multiple Sclerosis (MS):

Patients with MS regardless of the disease type, who experience severe fatigue will be eligible to participate.
Fatigue Severity Score of >/= 4.0 will qualify as long as all other inclusion / exclusion criteria are met.
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)

Exclusion Criteria for Healthy Volunteers:

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

Exclusion Criteria for Patients with Multiple Sclerosis (MS):

Adults unable to give informed consent due to cognitive impairment or mental disorders.
Children below the age of consent
Pregnant women
Prisoners
Systemic disorders known to cause fatigue such as severe anemia, infections, chronic systemic infectious or inflammatory disorders, including known autoimmune disorders.
Chronic fatigue syndrome
Hypothyroidism
Systemic malignancy
Undergoing chemotherapy
Depression
Sleep disorders including narcolepsy, excessive day-time sleep.
History of substance abuse
Excessive consumption of coffee or over-the-counter stimulants
Concomitant medications of amantadine, methylphenidate, amphetamines, pemoline, barbiturates, tizanidine, Monoamine oxidase inhibitor (MAO) inhibitors, benzodiazepines, barbiturates, tricyclic antidepressants, antihistamines, H2 blockers for gastro-esophageal reflux disease (GERD), selective serotonin reuptake inhibitors (SSRIs) and any other medication that in the opinion of the PI should be excluded.
Patients who were using modafinil for treatment of fatigues prior to the study may participate but will be required to undergo a washout of 2 weeks prior to entry into the trial.

Sites / Locations

University of Miami

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Histidine Intervention Group

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change extent of fatigue.

At the conclusion of the study, each individual would have completed a screening and baseline visit without any intervention and two weekly visits during intervention with the study medications. The two evaluations off drug will be compared to the two evaluations on drug. A drop of the Fatigue Severity Scale (FSS) score by 1 point or more will be considered a response. Once the information is converted into a binary function of response / no response, the data is amenable to conditional logistic regression analysis.

Change in Quality of life.

Multiple Sclerosis Quality of Life (MSQOL) scales will be used to measure the change in Quality of Life. Based on the scale, there will be a 0 to 100 with a higher score indicating a higher quality of life.

Change of fatigue impact scale.

Modified Fatigue Impact Scale (MFIS) scale will be used to evaluate the physical, cognitive and psychosocial scores. The score ranges from 0 to 84 with a lower score, lower side effects of fatigue.

Change of visual pain.

Visual analogue scale to evaluate the pain by using a numerical scale for 0 to 10 with a lower score, less visual pain.

Change of daytime sleepiness.

Epworth sleep scale to rate the probability of falling asleep during daytime on a scale of 0 to 24 with a lower score the lower the symptoms of sleepness.

Change of hunger sensitivity.

Hunger Satiety Scale to determine the extent of hunger and fullness by using a 1 to 10 score range with a higher score indicating a higher hunger sensitivity.

Full Information

NCT ID

NCT03266965

First Posted

July 4, 2017

Last Updated

October 5, 2020

Sponsor

University of Miami

Collaborators

United States Department of Defense

1. Study Identification

Unique Protocol Identification Number

NCT03266965

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

March 23, 2018 (Actual)

Primary Completion Date

August 7, 2020 (Actual)

Study Completion Date

August 7, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Miami

Collaborators

United States Department of Defense

4. Oversight

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

Data Monitoring Committee

Yes

5. Study Description

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

Detailed Description

Establish in an open label clinical trial the tolerability and safety of various doses of l-histidine and lodosyn that may increase levels of l-histidine and histamine in the serum and cerebrospinal fluid (CSF). Perform pharmacokinetic studies in serum and CSF of study subjects the levels of l-histidine and histamine after treatment with various combination of l-histidine and lodosyn. Preliminary information will also be collected on the effects of this intervention on alleviation of fatigue. The findings from this study go beyond the effects of histamine on fatigue. If central histamine can be increased by the strategy outlined above, a number of other vegetative hypothalamic functions intricately associated with fatigue including sleep, cognition and satiety need to be examined in MS patients in future studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

Fatigue, Histamine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Histidine Intervention Group

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Carbidopa

Other Intervention Name(s)

Lodosyn

Intervention Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

L-Histidine

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of adverse events experienced by participants.

Description

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.

Time Frame

30 days

Secondary Outcome Measure Information:

Title

Change extent of fatigue.

Description

At the conclusion of the study, each individual would have completed a screening and baseline visit without any intervention and two weekly visits during intervention with the study medications. The two evaluations off drug will be compared to the two evaluations on drug. A drop of the Fatigue Severity Scale (FSS) score by 1 point or more will be considered a response. Once the information is converted into a binary function of response / no response, the data is amenable to conditional logistic regression analysis.

Time Frame