Clinical trial NCT06795230: Blood Flow Restriction for Upper Limb Rehabilitation in People With Multiple Sclerosis. A Randomized Controlled Trial (BFRT-EM)
Official title: Effects of a Low-intensity Muscle Strengthening Protocol in Combination With Blood Flow Restriction Training on Upper Limb Impairment in People With Multiple Sclerosis. A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Multiple sclerosis
Upper limb
Rehabilitation
Blood Flow Restriction Training
Lead sponsor: Universidad Rey Juan Carlos
Sponsor class: OTHER
First posted: 2025-01-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Rehabilitation treatment. We do not use drugs or vaccines.
Primary purpose: OTHER

Brief summary: Although the Blood Flow Restriction Training (BFRT) system has attracted the attention of health professionals, research on this tool in people with neurological pathology, particularly multiple sclerosis (MS), is very limited. Furthermore, to our knowledge, studies on the effect of the BFRT system on forearm-hand muscle strength and fatigability, coordination and dexterity, functionality and quality of life in people with MS are nonexistent.

The main objective of our study are:

-To know the effects of low intensity training in combination with the BFRT system on upper limb strength and forearm and hand fatigability, dexterity, functionality and quality of life in people with MS.

Secondary Objectives

* To know if a low-intensity muscle strengthening program in combination with the BFRT system is superior to a conventional strengthening program.
* To know the adherence and satisfaction with the experimental intervention.

The investigators propose to conduct a randomized controlled trial (RCT) with examiner blinding with pre-intervention, post-intervention and follow-up assessment, following the recommendations of the CONSORT guidelines, designed to study the effects of the application of a low-intensity muscle strengthening program in combination with the BFRT system. This intervention will be carried out at the Leganés Multiple Sclerosis Association (ALEM). Patients will be randomly assigned through the GraphPad Software® QuickCalcs application to 2 study groups. A control group, which will receive a low intensity strengthening program in combination with the BFRT system; and an experimental group, which will receive a high intensity strengthening program.

Voluntary participation will be requested from patients diagnosed with MS in the Leganés Multiple Sclerosis Association (ALEM) who meet the inclusion criteria. Acceptance of the study and signature of the informed consent form will be required prior to the start of the program.

As this is the first study to evaluate the effectiveness and feasibility of a low-intensity muscle strengthening protocol in combination with BFRT on forearm and hand muscle strength and fatigability, coordination, dexterity, functionality and quality of life in people with MS, the sample size will be determined based on the most similar scientific literature possible. Hill et al developed an investigation comparing the adaptations of MS patients to two types of intervention: high intensity or conventional strengthening program versus low intensity in combination with BFRT. Since this is the only investigation to date that includes MMSS exercises in their intervention, we consider that the sample size proposed by Hill et al is the most appropriate for our investigation. The sample size obtained in that investigation was 19 subjects, so for the sample size of the present investigation a total of 19 subjects is proposed. However, estimating a 10% possible percentage of losses, we estimate a total of 21 total participants to be recruited.

Patients will be randomly assigned via the GraphPad Software® QuickCalcs application to 2 study groups. A control group, which will receive a low-intensity strengthening program in combination with the BFRT system; and an experimental group, which will receive a high-intensity strengthening program.

Detailed description: Among the different physical exercise modalities, Blood Flow Restriction Training (BFRT) appears. This type of approach is a training modality performed with occlusion of blood flow in the extremities, partially restricting arterial flow and venous return of blood to the muscles involved. It is usually, but not always, performed in parallel with LL-RT, with repetitions close to muscle fatigue in each set, however, it can also be performed in parallel with functional or task-focused training, such as horizontal walking, aerobic work on a stationary bike. BFRT is applied via an external pneumatic tourniquet at the proximal end of the upper or lower extremity, applying occlusion pressure that promotes ischemia and blood pooling in the capillary beds of the musculature distal to the tourniquet.

A 2020 investigation by Minitti et al indicated that the physiological mechanism behind the findings in muscle adaptations include acute muscle inflammation, increased recruitment of muscle fibers, decreased myostatins, decreased atrogenesis and satellite cell proliferation. Recent research has highlighted that the processes described above can be evoked in low-load strengthening in combination with the BFRT system, but not through conventional or high-load strengthening. In turn, these benefits have been observed in both young and older adults without increasing muscle damage, inflammation or pain perception.

In the field of physiotherapy, BFRT has gained increasing importance, as it has awakened interest in its application as a complement to therapeutic exercise, especially in those subjects who cannot tolerate high loads due to their clinical considerations. Its validity as a tool has been proven both for sports performance in different populations (elite or amateur athletes; young and older adults with no training experience), and in populations with pathology (older adults with fragility, musculoskeletal rehabilitation, post-surgical or post-immobilization conditions, femoropatellar syndromes, meniscus tears, ligamentous strains, rehabilitation after anterior cruciate ligament surgery, people with type 2 Diabetes Myelitus, people with neurological pathologies, including multiple sclerosis, MS).

The systematic review by Reina-Ruiz et al analyzed the effects of the use of the BFRT system in combination with LL-RT and aerobic exercise in people with different pathologies (anterior cruciate ligament reconstruction, stage two chronic kidney disease, coronary artery disease, end-stage renal disease, elderly comatose patients, knee osteoarthritis and recurrent non-specific low back pain). The results obtained in terms of strength, despite the heterogeneity of the outcome measures used, present the BFRT system as an effective tool for strength improvement, being equal or superior to HL-RT.

In a study conducted in 2022, Vinolo-Gil et al conducted a systematic review on the use of the BFRT system in populations with different neurological pathologies (spinal cord injury (SCI), stroke, cerebral palsy and MS). Their results showed improvements in sensorimotor function, frequency, gait length symmetry, gait speed and muscle thickness. However, no improvements in balance were found. The systematic review by Jønsson et al published in the current year 2024 reported that BFRT generated greater improvements in strength in people with inclusion body myositis compared to those who received no intervention and in subjects with incomplete spinal cord injury who performed the BFRT protocol in combination with functional electrical stimulation (FES), showing greater muscle circumference in the quadriceps than those who only received FES-based treatment, with unclear results in people with MS.

Given the idiosyncrasy of the tool, the safety of its use is a recurring theme in research, so a detailed analysis of the characteristics of the intervention is necessary. Since its origin in the 1980s, different types of cuffs have been used: pneumatic bicycle inner tubes, elastic bands and electronic devices. There is no scientific consensus on the use of one model over another; however, different investigations highlight certain determining characteristics for the safety and efficacy of the tool. The 4 main variables to take into account are: a) restriction pressure; b) cuff width; c) cuff type; d) cuff material.

Another major concern of researchers about the BFRT system is the pain that may result from an intervention with these characteristics, which has increased significantly in recent years in this regard.

The findings in terms of pain should be grouped into 2 sections: short term, medium term and long term. Short term: Korakakis et al analyzed the effects of an exercise protocol based on knee extension with low loads in combination with the BFRT system on anterior knee pain, observing that the 30 intervention subjects reduced their pain level in the 3 tests performed. In turn, the level of analgesia generated was maintained 45 minutes later, after a conventional physiotherapy session. Another investigation by Korakakis et al compared the effects of a low-intensity exercise protocol with a low-intensity exercise protocol in combination with the BFRT system. Analgesia in the low intensity and BFRT group was superior to that of the control group. Twenty percent of the participants in the control group reported greater discomfort after the intervention and 15% after 45 minutes. In turn, Lixandrão et al compared pain levels during and post-exercise compared to conventional training, finding no greater pain in the BFRT group. Medium and long term: Giles et al compared a low-load exercise protocol in combination with the BFRT system versus conventional training in patients with patellofemoral pain. The results showed significant differences in favor of the group that applied the BFRT system; in turn, the improvements were maintained in the follow-up assessment 6 months later.

Beyond pain, the potential adverse effects derived from the BFRT system have been investigated in different investigations, finding no adverse effects in people with neurological pathology according to the systematic review by Jønsson et al of 2024 or only minor adverse effects in populations without neurological pathology such as small hematomas, paresthesias, stiffness, pain or stiffness. According to Nakajima et al (50), from a population of 13,000 subjects without neurological pathology, serious adverse effects derived from an intervention through the BFRT system were extremely rare (0.008-0.055%), some of these being rhabdomyolysis or thromboembolism. With respect to serious adverse effects, it should be noted that the research by Minniti et al (22) presented similar findings in terms of the frequency of occurrence of adverse effects, however, they include an analysis of the cases that presented such serious adverse effects. One patient presented deep vein thrombosis (DVT) having been exposed to continuous occlusion for 30 - 60 minutes and presenting a history of edema and alterations of sensibility of several years of evolution. Two subjects presented rhabdomyolysis, the first had a history of DVT after ankle surgery and was exposed to an arbitrary compression of 100mmHg; the second patient showed no history or apparent risk factors, but the investigators do not know the information regarding the pressure applied and the duration of this. Finally, it is worth noting that in the first case, once he was medicated for the rhabdomyolysis and the patient continued with the experimental protocol without any other adverse effects.

Although the BFRT system has attracted the attention of health professionals, research on this tool in people with neurological pathology, particularly MS, is very limited. Furthermore, to our knowledge, studies on the effect of the BFRT system on forearm-hand muscle strength and fatigability, coordination and dexterity, functionality and quality of life in people with MS are nonexistent.

Eligibility criteria: Inclusion Criteria:

* \>18 years of age.
* Diagnosis of MS according to McDonald criteria (53) with a time of evolution longer than two years.
* Assessment on the Kurtzke Multiple Sclerosis Disability Status Scale (EDSS) with a score between 2. 0 (minimal disability in one section of the FS (at least one with a score of 2).) to 7.0 (unable to walk more than a few steps, even with assistance, basically confined to wheelchair and able to transfer from wheelchair to another place, or can manage to go to the toilet for 12 hours a day) .
* Stable medical treatment for at least six months prior to surgery.
* Upper extremity muscle tone no greater than 2 points (moderate hypertonia, increased muscle tone during most of the arc of motion, but can passively move the affected part with ease) on the modified Ashworth Scale.
* Muscle balance equal to or greater than 3 in the upper extremity.
* Score less than or equal to 4 points on the "Pyramidal Function" section of the EDSS functional scale.
* Absence of cognitive impairment, with ability to understand instructions and score equal to or greater than 24 on the Minimental Test.
* A score equal to or less than 2 points on the "Mental Functions" section of the EDSS.

Exclusion Criteria:

* Diagnosis of a neurological disease or musculoskeletal disorder other than MS.
* Diagnosis of a cardiovascular, respiratory or metabolic disease or other conditions that may interfere with this study.
* Having suffered an exacerbation or hospitalization in the last 3 months before starting the assessment protocol, or during the therapeutic intervention process.
* Having received a course of steroids, intravenous or oral, 6 months prior to the start of the assessment protocol and within the intervention period of the study duration.
* Having received treatment with botulinum toxin in the 6 months prior to the start of the study.
* A score higher than 2 points on the modified Ashworth scale.
* Cognitive or language impairment that prevents adequate communication or comprehension.
* Medical complications such as: history of deep vein thrombosis, pulmonary embolism, vascular disease, thrombophilia, or any circulatory or coagulation disorder.

Primary outcomes:
measure: Isometric prehensile hand strength (Kg)
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: Isometric pincer force (Kg)
timeFrame: Up to 8 weeks
measure: Gross coordination for the upper limb (Block and Box; number of cubes)
timeFrame: Up to 8 weeks
measure: Fine coordination for the upper limb (NHPT; time in seconds)
timeFrame: Up to 8 weeks
measure: Functional status of the upper limb (ABILHAND)
timeFrame: Up to 8 weeks
measure: Quality of life (MSIS-29)
timeFrame: Up to 8 weeks
measure: Satisfaction (CSQ8)
timeFrame: Up to 8 weeks
Other outcomes:
Locations:
city: Alcorcón
country: Spain
facility: Universidad Rey Juan Carlos
state: Madrid
Study officials:
affiliation: Universidad Rey Juan Carlos
name: Roberto Cano de la Cuerda, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References: