Multiple Sclerosis
Conditions
Keywords
Fatigue, Histamine
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.
Interventions
DRUGCarbidopa
All subjects will receive a fixed dose of 50mg of Lodosyn twice daily.
DIETARY_SUPPLEMENTL-Histidine
Sequential Dose Escalation of 250mg to 500mg to 1000mg twice daily.
Sponsors
United States Department of Defense
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
for Healthy Volunteers: 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. Inclusion Criteria for Patients with Multiple Sclerosis (MS): 1. Patients with MS regardless of the disease type, who experience severe fatigue will be eligible to participate. 2. Fatigue Severity Score of \>/= 4.0 will qualify as long as all other inclusion /
Exclusion criteria
are met. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events experienced by participants. | 30 days | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of life. | Screening(0 day), baseline(15 days) and final visit(30 days) | 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. | Screening(0 day), baseline(15 days) and final visit(30 days) | 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 extent of fatigue. | Screening(0 day), baseline(15 days) and final visit(30 days) | 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 of daytime sleepiness. | Screening(0 day), baseline(15 days) and final visit(30 days) | 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. | Screening(0 day), baseline(15 days) and final visit(30 days) | 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. |
| Change of visual pain. | Screening(0 day), baseline(15 days) and final visit(30 days) | Visual analogue scale to evaluate the pain by using a numerical scale for 0 to 10 with a lower score, less visual pain. |
Countries
United States
Outcome results
None listed