Amyotrophic Lateral Sclerosis, Cachexia, Huntington's Disease, Neurodegenerative Disease, Parkinson's Disease, Weight Loss
Conditions
Brief summary
This is a phase II feasibility, safety, tolerability and preliminary efficacy study of an e-Health application versus in-person nutritional counseling to maintain or increase weight in patients with neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Parkinson's Disease (PD) and Huntington's disease (HD). Primary Objectives include the feasibility, safety, tolerability and efficacy of an e-Health application to maintain or increase body weight compared to in-person nutritional counseling. Secondary Objectives are to measure the number of calories required to maintain or increase body weight in neurodegenerative diseases at all stages of the disease. Tertiary Objectives are to test the effects of an e-Health application compared to in-person nutritional counseling on disease progression using the ALSFRS-R, UHDRS or UDysRS, on survival, and on quality of life using the PROMIS SF v1.1 scale.
Detailed description
This is a single center, randomized, open-label, placebo controlled, parallel group study. The study treatment period is approximately 6 months and observation period is approximately 7 months. There are three parallel treatment groups: in-person nutritional counseling, nutritional counseling using an e-Health App, and standard care. Subjects will be randomly assigned in a 1:1:1 ratio using a computer-generated randomization scheme. Subjects in the two intervention arms will be given caloric recommendations designed to cause weight stability or modest weight gain, depending on their current BMI and weight loss history. All participants in the intervention arms will receive counseling either in-person or remotely through the App by registered dietitians (RD) working in the Bionutrition department of the Clinical Research Center at MGH. At MGH, approximately 150 ALS subjects (50 per treatment group) will be enrolled. Approximately 75-150 PD and HD subjects will enroll.
Interventions
BEHAVIORALIn-Person Nutritional Counseling by a Registered Dietitian
BEHAVIORALNutritional counseling using an e-Health Application
Sponsors
ALS Association
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults with neurodegenerative diseases such as ALS, PD or HD with or without a history of unintentional weight loss. 2. Male or female subjects aged 18 years or older. 3. Participants must be capable of providing informed consent and complying with trial procedures. 4. Participants must have an MGH swallowing screening tool score\>5 at the time of the screening visit 5. Participants or a designated caregiver must be able to obtain home weights and communicate to their RD
Exclusion criteria
1. Clinical evidence of unstable medical or psychiatric illness, in the investigator's judgment, which would prevent the participant from completing their assessments. 2. BMI \> 35 combined with a history of cardiovascular disease; or a history of diabetes regardless of BMI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimated Mean Change in Weight From Baseline to 6 Months | Change over time from Baseline to 6 months | The Primary Aim is to study the feasibility and efficacy to maintain or increase body weight of an e-Health application and in-person nutritional counseling compared to standard of care and to each other. Weights were measured in the clinic every 3 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Calorie Intake Over Time | Change from baseline over 6 months | Secondary aims include measuring the number of calories required to maintain or increase body weight in patients with neurodegenerative diseases. Total daily energy intake was calculated using 4 day food records at baseline, 3 months and 6 months |
| Safety: Frequency of Adverse Events | From baseline to month 7 (one month after 6 month end of study visit) | To study the safety of an e-Health application and in-person nutritional counseling compared to standard of care and to each other. |
| Tolerability: The Number of Participants Who Complete the Study While Complying With at Least 80% of the Counseling Sessions | Baseline, 3 months and 6 months | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Efficacy Measure: Disease Progression in ALS Functional Rating Scale-Revised (ALSFRS-R) | Change over time from Baseline to 6 months | Disease progression will be measured using disease-specific outcome measures (the ALSFRS-R scale). The range of the ALSFRS-R is 0-40 with higher scores indicating better function. Change in ALSFRS-R is reported as units/month. |
| Exploratory Efficacy Measure: Quality of Life | 18 months | Quality of life will be measured using the PROMIS SF 1.1 in units. |
| Exploratory Efficacy Measure: Survival | baseline to 18 months | Vital status will be measured until the last subject last visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| In-Person Nutritional Counseling Participants in the in-person nutritional counseling arm will meet with a Registered Dietitian at every clinic visit and will also receive regular phone calls to monitor weight and food intake. Participants' individual dietary needs will be calculated using baseline calorie consumption, weight history, disease status and current activity level.
In-Person Nutritional Counseling by a Registered Dietitian | 26 |
| E-Health App for Nutritional Counseling Participants randomized to the e-Health App arm with receive nutritional counseling using the e-Health Application. Participants will enter weights at home and complete electronic food records using the App. Participants' individual dietary needs will be calculated using baseline calorie consumption, weight history, disease status and current activity level. Participants will receive these calorie recommendations through the Application.
Nutritional counseling using an e-Health Application | 26 |
| Standard Care Participants are allowed to receive all usual treatments and medications. Participation in other research studies is allowed. | 26 |
| Total | 78 |
Baseline characteristics
| Characteristic | In-Person Nutritional Counseling | E-Health App for Nutritional Counseling | Standard Care | Total |
|---|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 11.9 | 54.7 years STANDARD_DEVIATION 11.5 | 57.5 years STANDARD_DEVIATION 10.9 | 56.9 years STANDARD_DEVIATION 11.5 |
| ALS Functional Rating Scale-Revised | 34.9 Total score in points STANDARD_DEVIATION 6.67 | 37.4 Total score in points STANDARD_DEVIATION 6.19 | 36.7 Total score in points STANDARD_DEVIATION 5.36 | 36.4 Total score in points STANDARD_DEVIATION 6.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 25 Participants | 24 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 26 Participants | 26 Participants | 26 Participants | 78 Participants |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 15 Participants | 31 Participants |
| Sex: Female, Male Male | 16 Participants | 20 Participants | 11 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 26 | 0 / 26 | 1 / 26 |
| other Total, other adverse events | 9 / 26 | 11 / 26 | 12 / 26 |
| serious Total, serious adverse events | 4 / 26 | 5 / 26 | 2 / 26 |
Outcome results
Primary
Estimated Mean Change in Weight From Baseline to 6 Months
The Primary Aim is to study the feasibility and efficacy to maintain or increase body weight of an e-Health application and in-person nutritional counseling compared to standard of care and to each other. Weights were measured in the clinic every 3 months.
Time frame: Change over time from Baseline to 6 months
Population: Please note that these are Parameter Estimates rather than means
| Arm | Measure | Value (MEAN) |
|---|---|---|
| In-Person Nutritional Counseling | Estimated Mean Change in Weight From Baseline to 6 Months | -0.1 kg |
| E-Health App for Nutritional Counseling | Estimated Mean Change in Weight From Baseline to 6 Months | -0.2 kg |
| Standard Care | Estimated Mean Change in Weight From Baseline to 6 Months | -1.2 kg |
Secondary
Change in Calorie Intake Over Time
Secondary aims include measuring the number of calories required to maintain or increase body weight in patients with neurodegenerative diseases. Total daily energy intake was calculated using 4 day food records at baseline, 3 months and 6 months
Time frame: Change from baseline over 6 months
Secondary
Safety: Frequency of Adverse Events
To study the safety of an e-Health application and in-person nutritional counseling compared to standard of care and to each other.
Time frame: From baseline to month 7 (one month after 6 month end of study visit)
Secondary
Tolerability: The Number of Participants Who Complete the Study While Complying With at Least 80% of the Counseling Sessions
Time frame: Baseline, 3 months and 6 months
Other Pre-specified
Exploratory Efficacy Measure: Disease Progression in ALS Functional Rating Scale-Revised (ALSFRS-R)
Disease progression will be measured using disease-specific outcome measures (the ALSFRS-R scale). The range of the ALSFRS-R is 0-40 with higher scores indicating better function. Change in ALSFRS-R is reported as units/month.
Time frame: Change over time from Baseline to 6 months
Population: Change over time of continuous, longitudinal measures was analyzed using a shared-baseline, mixed effect model with fixed effects for visit and an interaction between post-baseline visit and study arm and with a random slope and intercept for each subject with unstructured covariance.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| In-Person Nutritional Counseling | Exploratory Efficacy Measure: Disease Progression in ALS Functional Rating Scale-Revised (ALSFRS-R) | -5.8 units per month |
| E-Health App for Nutritional Counseling | Exploratory Efficacy Measure: Disease Progression in ALS Functional Rating Scale-Revised (ALSFRS-R) | -2.6 units per month |
| Standard Care | Exploratory Efficacy Measure: Disease Progression in ALS Functional Rating Scale-Revised (ALSFRS-R) | -5.2 units per month |
Other Pre-specified
Exploratory Efficacy Measure: Quality of Life
Quality of life will be measured using the PROMIS SF 1.1 in units.
Time frame: 18 months
Other Pre-specified
Exploratory Efficacy Measure: Survival
Vital status will be measured until the last subject last visit.
Time frame: baseline to 18 months