Histaminergic Basis of Fatigue in Multiple Sclerosis

NCT ID: NCT04764383

Last Updated: 2021-07-29

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2022-10-30

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).

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

PK/PD Group

Participants in the Pharmacokinetic (PK)/pharmacodynamic (PD) Group will receive L-Histidine and Lodosyn daily for 7 consecutive days.

Group Type: EXPERIMENTAL

L-Histidine

Intervention Type: DRUG

1000 mg capsules taken by mouth (PO) twice daily (BID).

Lodosyn

Intervention Type: DRUG

50 mg capsules taken PO BID.

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.

Group Type: PLACEBO_COMPARATOR

L-Histidine

Intervention Type: DRUG

1000 mg capsules taken by mouth (PO) twice daily (BID).

Placebo

Intervention Type: DRUG

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

Lodosyn

Intervention Type: DRUG

50 mg capsules taken PO BID.

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.

Group Type: EXPERIMENTAL

L-Histidine

Intervention Type: DRUG

1000 mg capsules taken by mouth (PO) twice daily (BID).

Placebo

Intervention Type: DRUG

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

Lodosyn

Intervention Type: DRUG

50 mg capsules taken PO BID.

Interventions

L-Histidine

1000 mg capsules taken by mouth (PO) twice daily (BID).

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Lodosyn

50 mg capsules taken PO BID.

Intervention Type: DRUG

Other Intervention Names

Histamine

Eligibility Criteria

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.

• 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)

Exclusion Criteria

For Healthy (Normal) Participants

• 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

• 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.

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

Sponsors

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

20201550

Identifier Type: -

Identifier Source: org_study_id