Multiple SclerosisPhase 1NCT03266965
Histaminergic Basis of Central Fatigue in Multiple Sclerosis - A Novel Approach
A Phase 1 study testing Carbidopa and L-Histidine in people with Multiple Sclerosis, run by University of Miami at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Carbidopa and L-Histidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Mar 2018to 7 Aug 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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)
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- Carbidopa, L-Histidine
- Keywords
- Fatigue, Histamine
- Medical subject headings
- Multiple Sclerosis, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarbidopaDrug
Also called Lodosyn
All subjects will receive a fixed dose of 50mg of Lodosyn twice daily.
L-HistidineDietary supplement
Sequential Dose Escalation of 250mg to 500mg to 1000mg twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Histidine Intervention Group | Experimental | 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. Receives: Drug: Carbidopa; Dietary Supplement: L-Histidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days
Secondary outcomes (6)
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.
Measured: Screening(0 day), baseline(15 days) and final visit(30 days)
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.
Measured: Screening(0 day), baseline(15 days) and final visit(30 days)
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.
Measured: Screening(0 day), baseline(15 days) and final visit(30 days)
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.
Measured: Screening(0 day), baseline(15 days) and final visit(30 days)
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.
Measured: Screening(0 day), baseline(15 days) and final visit(30 days)
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.
Measured: Screening(0 day), baseline(15 days) and final visit(30 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2017
- Study start23 Mar 2018
- Primary completion7 Aug 2020
- Study completion7 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Kottil W. Rammohan, University of Miami
- Investigators
- Kottil Rammohan, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03266965
- Sponsor's protocol ID
- 20161186
- Other IDs
- W81XWH-16-1-0462
- Status last verified
- Oct 2020
- First submitted
- 4 Jul 2017
- Last updated
- 8 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Histaminergic Basis of Central Fatigue in Multiple Sclerosis - A Novel Approach
- ClinicalTrials.gov ID
- NCT03266965
- Acronym / sponsor ID
- 20161186
- Conditions
- Multiple Sclerosis
- Keywords
- Fatigue, Histamine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 23 Mar 2018 (actual)
- Primary completion
- 7 Aug 2020 (actual)
- Study completion
- 7 Aug 2020 (actual)
- First posted
- 30 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Histidine Intervention Group | Experimental | Drug: Carbidopa, Dietary Supplement: L-HistidineA 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
- 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.
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarbidopaAlso: LodosynAll subjects will receive a fixed dose of 50mg of Lodosyn twice daily. | Drug | Histidine Intervention Group |
| L-HistidineSequential Dose Escalation of 250mg to 500mg to 1000mg twice daily. | Dietary supplement | Histidine Intervention Group |
Primary outcome
Number of adverse events experienced by participants.
Time frame: 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.
6 secondary outcomes
Change extent of fatigue.
Time frame: Screening(0 day), baseline(15 days) and final visit(30 days)
Change in Quality of life.
Time frame: Screening(0 day), baseline(15 days) and final visit(30 days)
Change of fatigue impact scale.
Time frame: Screening(0 day), baseline(15 days) and final visit(30 days)
Change of visual pain.
Time frame: Screening(0 day), baseline(15 days) and final visit(30 days)
Change of daytime sleepiness.
Time frame: Screening(0 day), baseline(15 days) and final visit(30 days)
Change of hunger sensitivity.
Time frame: Screening(0 day), baseline(15 days) and final visit(30 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kottil Rammohan, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carbidopa and L-Histidine in people with Multiple Sclerosis, run by University of Miami at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events experienced by participants. (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.