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

NCT ID: NCT03266965

Last Updated: 2020-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-23
• Study Completion Date: 2020-08-07

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

1. 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).

2. 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.

3. 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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Histidine Intervention Group

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.

Group Type: EXPERIMENTAL

Carbidopa

Intervention Type: DRUG

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

L-Histidine

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

Carbidopa

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

Intervention Type: DRUG

L-Histidine

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

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Lodosyn

Eligibility Criteria

Inclusion Criteria

1. Male or female subjects between the ages of 18 and 60 will be eligible.

2. Subjects should be in good physical health without history of chronic illness and should be generally considered healthy.

3. Spouses or caregivers of patients with MS would be encouraged to participate.

1. Patients with MS regardless of the disease type, who experience severe fatigue will be eligible to participate.

Exclusion Criteria

3. Established MS by McDonald Criteria - 2010 Revision (24). Relapse Remitting (RR) and progressive forms of MS are eligible

4. Severe fatigue that has lasted greater than 6 months

5. Clinically stable on a current therapy with any Disease Modifying Therapy (DMT)

1. Adults unable to give informed consent due to cognitive impairment or mental disorders.

2. Children below the age of consent

3. Pregnant women

4. Prisoners

5. History of chronic disorders like hypertension, diabetes, hyperlipidemia, depression, hypothyroidism etc. that require chronic treatment

6. Known chronic fatigue syndrome

7. Blood disorders or coagulopathy

8. Chronic allergies or history of asthma.

9. Using antihistamines, bronchodilators or H2 blockers for hyperacidity

10. Using medications for sleep, or known sleep disorders

11. Any medication or condition deemed unsuitable by the PI

1. Adults unable to give informed consent due to cognitive impairment or mental disorders.

2. Children below the age of consent

3. Pregnant women

4. Prisoners

5. Systemic disorders known to cause fatigue such as severe anemia, infections, chronic systemic infectious or inflammatory disorders, including known autoimmune disorders.

6. Chronic fatigue syndrome

7. Hypothyroidism

8. Systemic malignancy

9. Undergoing chemotherapy

10. Depression

11. Sleep disorders including narcolepsy, excessive day-time sleep.

12. History of substance abuse

13. Excessive consumption of coffee or over-the-counter stimulants

14. 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.

15. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Kottil W. Rammohan

Professor Of Clinical Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kottil Rammohan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

Other Identifiers

W81XWH-16-1-0462

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

20161186

Identifier Type: -

Identifier Source: org_study_id