Histaminergic Basis of Central Fatigue in Multiple Sclerosis - A Novel Approach
- Conditions
- Multiple Sclerosis
- Interventions
- Dietary Supplement: L-Histidine
- Registration Number
- NCT03266965
- Lead Sponsor
- University of Miami
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Histidine Intervention Group L-Histidine 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. Histidine Intervention Group Carbidopa 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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 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 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 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.
Trial Locations
- Locations (1)
University of Miami
🇺🇸Miami, Florida, United States