Neurofibromatosis 1
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTBlood draw
• An additional 10 mL of blood will then be drawn for mitochondrial testing purposes.
OTHERFACIT-F and Pain Scales
• Questionnaires regarding pain and fatigue will be provided for the subject to review and answer.
Sponsors
University of Arkansas
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
NF1 Group: Inclusion Criteria: * Diagnosed with NF1 Inclusion Criteria: * Not the first degree relative (biological parent, sibling, or child) of the NF1 patient who is in the NF1 group
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mitochondrial Respiration Efficiency (as Measured by OCR). | Baseline, Week 14, Week 28 | Mitochondrial respiration efficiency is measured here by the oxygen consumption rate (OCR) which is measured in units of picomoles per minute. |
| Mitochondrial Respiration Efficiency (as Measured by ECAR). | Baseline, Week 14, Week 28 | Mitochondrial respiration efficiency is measured here by the extracellular acidification rate (ECAR) which is measured in millipH per minute. |
| Vitamin D Levels | Baseline | 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. |
| Pain (as Measured With NRS-11 for Current Pain Over the Past 24 Hours) of NF1 Patients | Baseline, Week 14, Week 28 | 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). |
| Pain (as Measured With NRS-11 for Best Pain Over the Past 24 Hours) of NF1 Patients | Baseline, Week 14, Week 28 | 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). |
| Pain (as Measured With NRS-11 for Worst Pain Over the Past 24 Hours) of NF1 Patients | Baseline, Week 14, Week 28 | 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). |
| Fatigue (as Measured FACIT-F TOI) of NF1 Patients. | Baseline, Week 14, Week 28 | 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: 1. Physical Well-Being Subscale: Range 0-28, 2. Social/Family Well-Being Subscale: Range 0-28, 3. Emotional Well-Being Subscale: Range 0-24, 4. Functional Well-Being Subscale: Range 0-28, and 5. Fatigue Subscale: Range 0-52. The Trial Outcome Index (TOI) is the total score we chose to analyze. It consists of the sum of the Physical Well-Being Subscale, Functional Well-Being Subscale, and Fatigue Subscale and has a score range of 0-108. The higher the score, the better the quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 44 |
| 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. | 11 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 6 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | NF1 Group (Longitudinal Group) | Control Group (Cross-sectional Group) | Total |
|---|---|---|---|
| Age, Continuous | 43.55 years STANDARD_DEVIATION 15.22 | 47.08 years STANDARD_DEVIATION 12.93 | 44.26 years STANDARD_DEVIATION 14.75 |
| Extracellular Acidification Rate (ECAR) | 29.67 millipH/minute STANDARD_DEVIATION 9.13 | 19.85 millipH/minute STANDARD_DEVIATION 10.64 | 26.58 millipH/minute STANDARD_DEVIATION 10.54 |
| Functional Assessment of Chronic Illness Therapy (FACIT-F) - Fatigue | 71.9943 score on a scale STANDARD_DEVIATION 19.64485 | — | 71.9943 score on a scale STANDARD_DEVIATION 19.64485 |
| Oxygen Consumption Rate (OCR) | 67.71 picomole/minute STANDARD_DEVIATION 19.13 | 53.70 picomole/minute STANDARD_DEVIATION 24.09 | 63.31 picomole/minute STANDARD_DEVIATION 21.49 |
| Race/Ethnicity, Customized Race Black of African American | 6 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 1 Participants | 8 Participants | 9 Participants |
| Race/Ethnicity, Customized Race White | 36 Participants | 3 Participants | 39 Participants |
| Region of Enrollment United States | 44 participants | 11 participants | 55 participants |
| Sex: Female, Male Female | 31 Participants | 5 Participants | 36 Participants |
| Sex: Female, Male Male | 13 Participants | 6 Participants | 19 Participants |
| The Numeric Pain Rating Scale (NRS-11) Best | 1.95 score on a scale STANDARD_DEVIATION 2.605 | — | 1.95 score on a scale STANDARD_DEVIATION 2.605 |
| The Numeric Pain Rating Scale (NRS-11) Current | 2.70 score on a scale STANDARD_DEVIATION 3.137 | — | 2.70 score on a scale STANDARD_DEVIATION 3.137 |
| The Numeric Pain Rating Scale (NRS-11) Worst | 4.77 score on a scale STANDARD_DEVIATION 3.634 | — | 4.77 score on a scale STANDARD_DEVIATION 3.634 |
| Vitamin D | 33.666 nanogram/milliliter STANDARD_DEVIATION 13.8982 | — | 33.666 nanogram/milliliter STANDARD_DEVIATION 13.8982 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
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: 1. Physical Well-Being Subscale: Range 0-28, 2. Social/Family Well-Being Subscale: Range 0-28, 3. Emotional Well-Being Subscale: Range 0-24, 4. Functional Well-Being Subscale: Range 0-28, and 5. Fatigue Subscale: Range 0-52. The Trial Outcome Index (TOI) is the total score we chose to analyze. It consists of the sum of the Physical Well-Being Subscale, Functional Well-Being Subscale, and Fatigue Subscale and has a score range of 0-108. The higher the score, the better the quality of life.
Time frame: Baseline, Week 14, Week 28
Population: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NF1 Group (Longitudinal Group) | Fatigue (as Measured FACIT-F TOI) of NF1 Patients. | Baseline | 71.9943 Questionnaire score | Standard Deviation 19.64485 |
| NF1 Group (Longitudinal Group) | Fatigue (as Measured FACIT-F TOI) of NF1 Patients. | Week 14 | 73.1752 Questionnaire score | Standard Deviation 17.31894 |
| NF1 Group (Longitudinal Group) | Fatigue (as Measured FACIT-F TOI) of NF1 Patients. | Week 28 | 75.3935 Questionnaire score | Standard Deviation 21.9713 |
p-value: 0.88Spearman's Rho
p-value: 0.53Spearman's Rho
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.
Time frame: Baseline, Week 14, Week 28
Population: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NF1 Group (Longitudinal Group) | Mitochondrial Respiration Efficiency (as Measured by ECAR). | Baseline | 29.6667 millipH/minute | Standard Deviation 9.13282 |
| NF1 Group (Longitudinal Group) | Mitochondrial Respiration Efficiency (as Measured by ECAR). | Week 14 | 32.4583 millipH/minute | Standard Deviation 11.65965 |
| NF1 Group (Longitudinal Group) | Mitochondrial Respiration Efficiency (as Measured by ECAR). | Week 28 | 33.0467 millipH/minute | Standard Deviation 7.8799 |
| Control Group (Cross-sectional Group) | Mitochondrial Respiration Efficiency (as Measured by ECAR). | Baseline | 19.8500 millipH/minute | Standard Deviation 10.64305 |
p-value: 0.54Spearman's Rho
p-value: 0.36Spearman's Rho
p-value: 0.94Spearman's Rho
p-value: 0.53Spearman's Rho
p-value: 0.51Spearman's Rho
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.
Time frame: Baseline, Week 14, Week 28
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NF1 Group (Longitudinal Group) | Mitochondrial Respiration Efficiency (as Measured by OCR). | Baseline | 67.7167 picomole/minute | Standard Deviation 19.13264 |
| NF1 Group (Longitudinal Group) | Mitochondrial Respiration Efficiency (as Measured by OCR). | Week 14 | 73.3358 picomole/minute | Standard Deviation 22.92499 |
| NF1 Group (Longitudinal Group) | Mitochondrial Respiration Efficiency (as Measured by OCR). | Week 28 | 68.5789 picomole/minute | Standard Deviation 17.76314 |
| Control Group (Cross-sectional Group) | Mitochondrial Respiration Efficiency (as Measured by OCR). | Baseline | 53.7000 picomole/minute | Standard Deviation 24.0851 |
p-value: <0.01Spearman's Rho
p-value: 0.02Spearman's Rho
p-value: 0.03Spearman's Rho
p-value: 0.88Spearman's Rho
p-value: 0.36Spearman's Rho
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).
Time frame: Baseline, Week 14, Week 28
Population: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NF1 Group (Longitudinal Group) | Pain (as Measured With NRS-11 for Best Pain Over the Past 24 Hours) of NF1 Patients | Baseline | 1.95 Questionnaire score | Standard Deviation 2.605 |
| NF1 Group (Longitudinal Group) | Pain (as Measured With NRS-11 for Best Pain Over the Past 24 Hours) of NF1 Patients | Week 14 | 1.41 Questionnaire score | Standard Deviation 2.403 |
| NF1 Group (Longitudinal Group) | Pain (as Measured With NRS-11 for Best Pain Over the Past 24 Hours) of NF1 Patients | Week 28 | 1.53 Questionnaire score | Standard Deviation 2.324 |
p-value: 0.02Spearman's Rho
p-value: 0.36Spearman's Rho
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).
Time frame: Baseline, Week 14, Week 28
Population: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NF1 Group (Longitudinal Group) | Pain (as Measured With NRS-11 for Current Pain Over the Past 24 Hours) of NF1 Patients | Baseline | 2.70 Questionnaire score | Standard Deviation 3.137 |
| NF1 Group (Longitudinal Group) | Pain (as Measured With NRS-11 for Current Pain Over the Past 24 Hours) of NF1 Patients | Week 14 | 2.05 Questionnaire score | Standard Deviation 3.077 |
| NF1 Group (Longitudinal Group) | Pain (as Measured With NRS-11 for Current Pain Over the Past 24 Hours) of NF1 Patients | Week 28 | 1.78 Questionnaire score | Standard Deviation 2.706 |
p-value: <0.01Spearman's Rho
p-value: 0.54Spearman's Rho
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).
Time frame: Baseline, Week 14, Week 28
Population: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NF1 Group (Longitudinal Group) | Pain (as Measured With NRS-11 for Worst Pain Over the Past 24 Hours) of NF1 Patients | Baseline | 4.77 Questionnaire score | Standard Deviation 3.634 |
| NF1 Group (Longitudinal Group) | Pain (as Measured With NRS-11 for Worst Pain Over the Past 24 Hours) of NF1 Patients | Week 14 | 3.38 Questionnaire score | Standard Deviation 3.951 |
| NF1 Group (Longitudinal Group) | Pain (as Measured With NRS-11 for Worst Pain Over the Past 24 Hours) of NF1 Patients | Week 28 | 2.61 Questionnaire score | Standard Deviation 3.433 |
p-value: 0.03Spearman's Rho
p-value: 0.94Spearman's Rho
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.
Time frame: Baseline
Population: The analysis population was determined by how many vitamin D level values were found in the medical records of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NF1 Group (Longitudinal Group) | Vitamin D Levels | 33.665909090909 nanogram/milliliter | Standard Deviation 13.898183638758 |
p-value: 0.36Spearman's Rho
p-value: 0.51Spearman's Rho