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Neurofibromatosis type 1 is a common genetic disease with a broad spectrum of clinical manifestations in multiple organs of the body. This project will study the (dys)function of mitochondria in patients with neurofibromatosis through multiple collections of blood samples from patients and people not afflicted by neurofibromatosis (control group). This study will evaluate how the function of mitochondria changes with time and if medications and supplements can influence the function of the mitochondria. Patients will also answer questions regarding symptoms like fatigue and pain.
Neurofibromatosis type 1 is a common genetic disease with a broad spectrum of clinical manifestations in multiple organs of the body. Some of those symptoms are skin lesions, tumors and cancers, as also pain, and fatigue. In animal models of this disease, dysfunction of mitochondria, a part of the cell which is responsible for energy production, is often described. This project will study the (dys)function of mitochondria in patients with neurofibromatosis through multiple collections of blood samples from patients and people not afflicted by neurofibromatosis (control group). Those blood samples will be used to run tests that analyses the function of the mitochondria and compare the results from the neurofibromatosis group with the control group. As multiple samples from the same patient will be tested in different times, this study will evaluate how the function of mitochondria changes with time and if medications and supplements can influence the function of the mitochondria. Patients will also answer questions regarding symptoms like fatigue and pain. Doing so, the investigator plan to confirm mitochondrial dysfunction in patients, if the degree of dysfunction correlates with symptoms like pain and fatigue, and if supplements and medication like MEK inhibitors that patients with neurofibromatosis type 1 use in a daily basis modulates (for better or worse) a pre-existing mitochondrial dysfunction.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NF1 Group | This study will look to enroll 40 to 45 adults over 18 years old diagnosed with NF1. |
| |
| Control Group | This study will look to enroll 10 to 15 adults over 18 years old without NF1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood draw | Diagnostic Test | • An additional 10 mL of blood will then be drawn for mitochondrial testing purposes. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mitochondrial Respiration Efficiency (as Measured by OCR). | Mitochondrial respiration efficiency is measured here by the oxygen consumption rate (OCR) which is measured in units of picomoles per minute. | Baseline, Week 14, Week 28 |
| Mitochondrial Respiration Efficiency (as Measured by ECAR). | Mitochondrial respiration efficiency is measured here by the extracellular acidification rate (ECAR) which is measured in millipH per minute. | Baseline, Week 14, Week 28 |
| Vitamin D Levels | We hypothesize that mitochondrial dysfunction among NF1 patients sensitizes them to therapeutic interventions targeting mitochondria. We will assess the impact of vitamin D treatment to potentially improve mitochondrial function as measured by OCR. Vitamin D is measured in units of nanogram per milliliter. | Baseline |
| Pain (as Measured With NRS-11 for Current Pain Over the Past 24 Hours) of NF1 Patients | The NF1 clinical symptom of pain as measured with The Numeric Pain Rating Scale (NRS-11) for current pain over the past 24 hours (min=0, max=10, higher score = more pain). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). | Baseline, Week 14, Week 28 |
| Pain (as Measured With NRS-11 for Best Pain Over the Past 24 Hours) of NF1 Patients | The NF1 clinical symptom of pain as measured with The Numeric Pain Rating Scale (NRS-11) for best pain over the past 24 hours (min=0, max=10, higher score = more pain). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). | Baseline, Week 14, Week 28 |
| Pain (as Measured With NRS-11 for Worst Pain Over the Past 24 Hours) of NF1 Patients |
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NF1 Group:
Inclusion Criteria:
Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Erika Santos Horta, MD | University of Arkansas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas For Medical Sciences | Little Rock | Arkansas | 72205 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | NF1 Group (Longitudinal Group) | This study will look to enroll 40 to 45 adults over 18 years old diagnosed with NF1. Participants will have SOC labs and an additional 10 mL of blood drawn for mitochondrial testing purposes at Baseline, Week 14, and Week 28. At these same 3 timepoints, measures of fatigue (FACIT-F QoL) and pain (Numeric Pain Rating QoL) will be provided for the participant to review and answer. A medical history will be taken at Baseline only. |
| FG001 | Control Group (Cross-sectional Group) | These participants are assessed only at consent, 10 mL of blood will be drawn for mitochondrial testing purposes. They will not receive fatigue or pain measures. Their medical history will not be taken. They will not receive SOC labs. This study will look to enroll 10 to 15 adults over 18 years old without NF1. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | NF1 Group (Longitudinal Group) | Participants will have SOC labs and an additional 10 mL of blood drawn for mitochondrial testing purposes at Baseline, Week 14, and Week 28. At these same 3 timepoints, measures of fatigue (FACIT-F QoL) and pain (Numeric Pain Rating QoL) will be provided for the participant to review and answer. A medical history will be taken at Baseline only. This study will look to enroll 40 to 45 adults over 18 years old diagnosed with NF1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mitochondrial Respiration Efficiency (as Measured by OCR). | Mitochondrial respiration efficiency is measured here by the oxygen consumption rate (OCR) which is measured in units of picomoles per minute. | The analysis population was determined by how many OCR values (corresponding to blood samples) we had for each visit. We had 24 values for Visit 1, 40 for Visit 2, and 30 for Visit 3 (24+40+30=94). This had to do with logistics (getting blood samples, using the Seahorse XF Bioanalyzer). For the control group, which only had a single blood draw, there were 11 blood samples. | Posted | Mean | Standard Deviation | picomole/minute | Baseline, Week 14, Week 28 | blood sample | blood sample |
|
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Deaths, serious adverse events, and nonserious adverse events were not assessed for study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NF1 Group | This study will look to enroll 40 to 45 adults over 18 years old diagnosed with NF1. Blood draw: • An additional 10 mL of blood will then be drawn for mitochondrial testing purposes. FACIT-F and Pain Scales: • Questionnaires regarding pain and fatigue will be provided for the subject to review and answer. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| I-Shin Wen | University of Arkansas for Medical Sciences | 5016868274 | 24024 | IWen@uams.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 18, 2023 | Mar 13, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009456 | Neurofibromatosis 1 |
| ID | Term |
|---|---|
| D017253 | Neurofibromatoses |
| D009455 | Neurofibroma |
| D018317 | Nerve Sheath Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Blood samples will be collected from patients and controls during routine appointments.
| FACIT-F and Pain Scales | Other | • Questionnaires regarding pain and fatigue will be provided for the subject to review and answer. |
|
The NF1 clinical symptom of pain as measured with The Numeric Pain Rating Scale (NRS-11) for worst pain over the past 24 hours (min=0, max=10, higher score = more pain). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). |
| Baseline, Week 14, Week 28 |
| Fatigue (as Measured FACIT-F TOI) of NF1 Patients. | The NF1 clinical symptom of fatigue as measured with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). The FACIT-F asks respondents to rate items on a scale from 0 to 4. There are 5 subscales with varying possible ranges (due to varying numbers of items) as follows:
The higher the score, the better the quality of life. | Baseline, Week 14, Week 28 |
| Withdrawal by Subject |
|
| BG001 | Control Group (Cross-sectional Group) | These participants are assessed only at consent, 10 mL of blood will be drawn for mitochondrial testing purposes. They will not receive fatigue or pain measures. Their medical history will not be taken. They will not receive SOC labs. This study will look to enroll 10 to 15 adults over 18 years old without NF1. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Oxygen Consumption Rate (OCR) | Mitochondrial respiration efficiency of PBMCs is measured here by the oxygen consumption rate (OCR) in picomoles/minute. | Not all 44 participants with NF1 had OCR values due to timing issues with the blood samples and use of the Seahorse XF bioanalyzer. There were 24 usable blood samples from 24 participants. | Mean | Standard Deviation | picomole/minute |
|
| Extracellular Acidification Rate (ECAR) | Mitochondrial respiration efficiency of PBMCs is measured here by the extracellular acidification rate (ECAR) in millipH/minute. | Not all 44 participants with NF1 had OCR values due to the logistics of getting blood samples in time to use the Seahorse XF bioanalyzer. There were 24 usable blood samples from 24 participants. | Mean | Standard Deviation | millipH/minute |
|
| The Numeric Pain Rating Scale (NRS-11) Current | The Numeric Pain Rating Scale (NRS-11) asks respondents to make 3 pain ratings (on a scale from 0 to 10, with higher scores indicating greater pain), corresponding to their current pain, their best pain experienced over 24 hours, and their worst pain experienced over 24 hours. This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). This study-specific baseline measure is the measure of current pain for participants with NF1. | Control participants were not asked to complete this measure. | Mean | Standard Deviation | score on a scale |
|
| The Numeric Pain Rating Scale (NRS-11) Best | The Numeric Pain Rating Scale (NRS-11) asks respondents to make 3 pain ratings(on a scale from 0 to 10, with higher scores indicating greater pain), corresponding to their current pain, their best pain experienced over 24 hours, and their worst pain experienced over 24 hours. This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). This study-specific measure is the measure of the best pain experienced over 24 hours for participants with NF1. | Control participants were not asked to complete this measure. | Mean | Standard Deviation | score on a scale |
|
| The Numeric Pain Rating Scale (NRS-11) Worst | The Numeric Pain Rating Scale (NRS-11) asks respondents to make 3 pain ratings (on a scale from 0 to 10, with higher scores indicating greater pain), corresponding to their current pain, their best pain experienced over 24 hours, and their worst pain experienced over 24 hours. This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). This study-specific baseline measure is the measure of worst pain experienced over 24 hours for participants with NF1. | Control participants were not asked to complete this measure. | Mean | Standard Deviation | score on a scale |
|
| Functional Assessment of Chronic Illness Therapy (FACIT-F) - Fatigue | The NF1 clinical symptom of fatigue is measured with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). | The control participants were not asked to complete this measure. | Mean | Standard Deviation | score on a scale |
|
| Vitamin D | The impact of vitamin D treatment to potentially improve mitochondrial function was assessed in units of nanogram/milliliter. | The vitamin D levels for control participants were not measured. | Mean | Standard Deviation | nanogram/milliliter |
|
| OG001 | Control Group (Cross-sectional Group) | These participants are assessed only at consent, 10 mL of blood will be drawn for mitochondrial testing purposes (OCR and ECAR). They will not receive fatigue (FACIT-F) or pain (NRS-11) measures. Their medical history will not be taken (vitamin D levels). They will not receive SOC labs. This study will look to enroll 10 to 15 adults over 18 years old without NF1. |
|
|
|
| Primary | Mitochondrial Respiration Efficiency (as Measured by ECAR). | Mitochondrial respiration efficiency is measured here by the extracellular acidification rate (ECAR) which is measured in millipH per minute. | The analysis population was determined by how many ECAR values (corresponding to blood samples) we had for each visit. We had 24 values for Visit 1, 40 for Visit 2, and 30 for Visit 3 (24+40+30=94). This had to do with logistics (getting blood samples, using the Seahorse XF Bioanalyzer). | Posted | Mean | Standard Deviation | millipH/minute | Baseline, Week 14, Week 28 | blood sample | blood sample |
|
|
|
|
| Primary | Vitamin D Levels | We hypothesize that mitochondrial dysfunction among NF1 patients sensitizes them to therapeutic interventions targeting mitochondria. We will assess the impact of vitamin D treatment to potentially improve mitochondrial function as measured by OCR. Vitamin D is measured in units of nanogram per milliliter. | The analysis population was determined by how many vitamin D level values were found in the medical records of participants. | Posted | Mean | Standard Deviation | nanogram/milliliter | Baseline |
|
|
|
|
| Primary | Pain (as Measured With NRS-11 for Current Pain Over the Past 24 Hours) of NF1 Patients | The NF1 clinical symptom of pain as measured with The Numeric Pain Rating Scale (NRS-11) for current pain over the past 24 hours (min=0, max=10, higher score = more pain). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). | The analysis population was determined by how many participants completed the NRS-11 for each visit. We had 44 values for Visit 1, 39 for Visit 2, and 36 for Visit 3 (44+39+36=119). | Posted | Mean | Standard Deviation | Questionnaire score | Baseline, Week 14, Week 28 | Questionnaire score | Questionnaire score |
|
|
|
|
| Primary | Pain (as Measured With NRS-11 for Best Pain Over the Past 24 Hours) of NF1 Patients | The NF1 clinical symptom of pain as measured with The Numeric Pain Rating Scale (NRS-11) for best pain over the past 24 hours (min=0, max=10, higher score = more pain). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). | The analysis population was determined by how many participants completed the NRS-11 for each visit. We had 44 values for Visit 1, 39 for Visit 2, and 36 for Visit 3 (44+39+36=119). | Posted | Mean | Standard Deviation | Questionnaire score | Baseline, Week 14, Week 28 | Questionnaire score | Questionnaire score |
|
|
|
|
| Primary | Pain (as Measured With NRS-11 for Worst Pain Over the Past 24 Hours) of NF1 Patients | The NF1 clinical symptom of pain as measured with The Numeric Pain Rating Scale (NRS-11) for worst pain over the past 24 hours (min=0, max=10, higher score = more pain). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). | The analysis population was determined by how many participants completed the NRS-11 for each visit. We had 44 values for Visit 1, 39 for Visit 2, and 36 for Visit 3 (44+39+36=119). | Posted | Mean | Standard Deviation | Questionnaire score | Baseline, Week 14, Week 28 | Questionnaire score | Questionnaire score |
|
|
|
|
| Primary | Fatigue (as Measured FACIT-F TOI) of NF1 Patients. | The NF1 clinical symptom of fatigue as measured with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). The FACIT-F asks respondents to rate items on a scale from 0 to 4. There are 5 subscales with varying possible ranges (due to varying numbers of items) as follows:
The higher the score, the better the quality of life. | The analysis population was determined by how many participants completed the FACIT-F for each visit. We had 44 values for Visit 1, 39 for Visit 2, and 36 for Visit 3 (44+39+36=119). | Posted | Mean | Standard Deviation | Questionnaire score | Baseline, Week 14, Week 28 | Questionnaire score | Questionnaire score |
|
|
|
|
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Control Group | This study will look to enroll 10 to 15 adults over 18 years old without NF1. Blood draw: • An additional 10 mL of blood will then be drawn for mitochondrial testing purposes. | 0 | 0 | 0 | 0 | 0 | 0 |
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| D009370 |
| Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009386 | Neoplastic Syndromes, Hereditary |
| D020752 | Neurocutaneous Syndromes |
| D009422 | Nervous System Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| Other |
|
| Unknown or Not Reported |
|
|
|
|
| Week 14 |
|
|
| Week 28 |
|
|
Spearman's rho used to analyze correlation between ECAR (Extracellular Acidification Rate) and NRS-11 Best (Numeric Pain Rating Scale for best pain).
| 0.36 |
| Other |
| Spearman's Rho | Spearman's rho used to analyze correlation between ECAR (Extracellular Acidification Rate) & NRS-11 Worst (Numeric Pain Rating Scale for worst pain). | 0.94 | Other |
| Spearman's Rho | Correlation: ECAR (Extracellular Acidification Rate) & FACIT-F TOI (Functional Assessment of Chronic Illness Therapy - Fatigue, Trial Outcome Index). | 0.53 | Other |
| Spearman's Rho | Spearman's rho was used to analyze correlation between ECAR (Extracellular Acidification Rate) and vitamin D levels. | 0.51 | Other |
| 0.51 |
| Other |
|
| Week 14 |
|
|
| Week 28 |
|
|
Spearman's rho used analyze correlation between ECAR (Extracellular Acidification Rate) & NRS-11 Current (Numeric Pain Rating Scale for current pain).
| 0.54 |
| Other |
|
| Week 14 |
|
|
| Week 28 |
|
|
Spearman's rho used to analyze correlation between ECAR (Extracellular Acidification Rate) and NRS-11 Best (Numeric Pain Rating Scale for best pain).
| 0.36 |
| Other |
|
| Week 14 |
|
|
| Week 28 |
|
|
Spearman's rho used to analyze correlation between ECAR (Extracellular Acidification Rate) & NRS-11 Worst (Numeric Pain Rating Scale for worst pain).
| 0.94 |
| Other |
|
| Week 14 |
|
|
| Week 28 |
|
|
Correlation: ECAR (Extracellular Acidification Rate) & FACIT-F TOI (Functional Assessment of Chronic Illness Therapy - Fatigue, Trial Outcome Index).
| 0.53 |
| Other |