Osmotin Plant Protein for Progressive Multiple Sclerosis

Study Overview
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Brief Summary
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The aim of this study is to explore the anti-inflammatory and neuroprotective effects of a novel nutraceutical product (commercial name Forza™️), consisting of the plant osmotin protein, in patients with progressive multiple sclerosis (PMS). The potential effect on brain metabolism and microstructure will be evaluated by magnetic resonance imaging (MRI) performed six months before starting treatment, at baseline, and after one and six months of treatment. At the same timepoints, electrophysiology, neurofilaments (NfL) quantification, optical coherence tomography (OCT) and clinical assessments will be performed.

Official Title
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Exploratory Trial of Forza™️, a Novel Nutraceutical From Actinidia Deliciosa Plants Bioengineered to Bio-encapsulate the Osmotin Plant Protein as Adjuvant for the Treatment of Progressive Multiple Sclerosis

Conditions
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Progressive Multiple Sclerosis

Intervention / Treatment
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* Dietary Supplement: Osmotin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Diagnosis of progressive multiple sclerosis (PMS) Expanded Disability Status Scale EDSS ≤ 6.5 Exclusion Criteria: Contraindications to MRI Pregnancy HIV positivity Severe renal, hepatic, oncological, hematological and psychiatric diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Osmotin<br>Administration of a nutraceutical supplement provided in capsules, that consists of lyophilised and pulverised kiwi leaves from bioengineered kiwi (Actinidia Deliciosa) plants overexpressing the tobacco protein Osmotin. | Dietary Supplement: Osmotin<br>* Oral administration for 6 months of 7 capsules per day (4 in the morning and 3 in the evening) for a daily dosage of 5 grams.<br>* Other names: FORZA™️;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-related adverse events after 1 month of therapy. |  | 1 month (after 1 month of treatment). | 
| Incidence and severity of treatment-related adverse events after 6 months of therapy. |  | 6 months (after 6 months of treatment). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Expanded Disability Status Scale (EDSS). | The EDSS score ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. | 12 months (6 month before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in Timed 25 Foot Walk (T25FW). | Quantitative mobility and leg function performance test based on a timed 25-walk. T25FW improvement is ≥15% decrease in time from first record and worsening is ≥15% increase in time from first record. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in 12-item Multiple Sclerosis Walking Scale (MSWS12). | Self-reported measure of the impact of Multiple Sclerosis on the individual's walking ability. The scoring provides 1-5 for each of the 12 items, with 1 meaning no limitations and 5 meaning extreme limitation, for a maximum total score of 60. Then, this total score is transformed to a scale with a range from 0 to 100. Higher scores indicate a greater impact on walking than lower scores. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in Nine-Hole Peg Test (9HPT). | Quantitative measure of upper extremity (arm and hand) function. 9HPT improvement is ≥15% decrease in time from first record and worsening is ≥15% increase in time from first record. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in Montreal Cognitive Assessment (MOCA). | Test to assesses different cognitive dimensions including attention and concentration, executive functions, memory, language, visuospatial skills, abstract thinking, calculation, and orientation. The lowest score that can be obtained from the scale is 0, and the highest score is 30. Higher scores indicate a better cognitive levels. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in Symbol Digit Modalities Test (SDMT). | Test to assess cognitive processes including memory, lexical access speed and information processing speed. The score is the number of correct answers in 90 seconds. The total score ranged from 0 to 110. Higher values represent better outcome. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in patient self-evaluation of depression and anxiety recorded with Hospital Anxiety Depression Scale (HADS). | Hospital Anxiety Depression Scale (HADS) is a 14 item questionnaire which consists two sub-scale evaluating anxiety (HADS-A) and depression (HADS-D). HADS-A sub-scale has seven items and each item is scored on a scale of 0 to 3. Total sub-scale score ranged from 0 to 21. Higher score mean a worse outcome. HADS-D sub-scale has seven items and each item is scored on a scale of 0 to 3. Total score ranged from 0 to 21. Higher scores reflects more severe depression. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in bladder domain function recorded with Overactive Bladder (OAB) questionnaire. | Self-reported questionnaire to quantify Overactive Bladder symptoms including urgency, urination, frequent urination and feeling of urine at night and waking up. The scale consists of 8 items and answers are scored on a 6-level Likert scale. A maximum score of 40 can be obtained from the scale, and a score below 8 eliminates overactive bladder. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| The impact of Forza™️ on neurophysiology in PMS. | Motor evoked potentials (MEPs), somatosensory evoked potentials (SEPs), visual evoked potentials (VEPs) will be measured and compared pre and post treatment. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| The impact of Forza™️ on retinal atrophy in PMS. | Optical Coherence Tomography (OCT) will be measured and compared pre and post treatment to assess the retinal thickness. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in serum neurofilament Light Chain (NfL) levels to verify the neuroprotective action of Forza™️ in PMS. |  | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in brain metabolism as concentration of glutamate, N-acetylaspartate, creatine and choline. | Proton magnetic resonance spectroscopy (1H-MRI) will be performed to quantify brain glutamate, N-acetylaspartate, creatine and choline. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 
| Change in brain microstructure. | Brain magnetic resonance imaging (MRI) will be performed with a multi-shell diffusion-weighted (DWI) sequence. | 12 months (6 months before starting treatment, at baseline and both after one month and six months of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osmotin