Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000844549
Ethics application status
Approved
Date submitted
14/05/2024
Date registered
8/07/2024
Date last updated
8/07/2024
Date data sharing statement initially provided
8/07/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Effects of a Three-week Exercises Program in Patients with Diabetic Polyneuropathy: Randomized Controlled Trial
Scientific title
The Effects of a Supervised Three-week Exercises Program on Range of Motion and Muscle Strength in Lower Leg and Foot, Gait Parameters, Distribution of Pressure and Force on the Ground During Walking and Sensation in Patients with Diabetic Polyneuropathy: Randomized, Two arm, Parallel, Open Label, Controlled Trial
Secondary ID [1] 312148 0
Nil known
Universal Trial Number (UTN)
U1111-1307-8771
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic polyneuropathy 333793 0
Condition category
Condition code
Metabolic and Endocrine 330464 330464 0 0
Diabetes
Physical Medicine / Rehabilitation 330465 330465 0 0
Physiotherapy
Neurological 330831 330831 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Brief name: Exercise program

Patients in the intervention group received alpha-lipoic acid intravenously at a dose of 600 mg dissolved in 250 ml of 0.9% sodium chloride solution, administered over 60 minutes once a day for 15 consecutive therapy days, excluding weekends.
Additionally, they participated in a 50–60-minute daily exercise program for 15 consecutive therapy days, excluding weekends.

The intervention comprised a specific one-on-one kinesiotherapy program consisting of four exercise blocks, each targeting different objectives: (a) increasing foot and ankle range of motion, (b) strengthening foot and ankle muscles, (c) performing functional (balance) exercises and (d) training walking skills and foot rollover.
Each session was composed of some of the exercises from the four exercise blocks.
Gradual and progressive difficulty is offered to the patient, respecting any limitation due to pain and/or decrease in performance during execution. In addition, in each session, the exercises were performed following an order that starts with the passive exercises, progresses to active, and finishes with walking and functional skills.
The exercises were individually adjusted to each patient, guided and supervised by a physiotherapist.
The intensity and speed of performing the exercises are adjusted to prevent pain and discomfort during execution. Each exercise was performed for a specified number of repetitions as described below.
After the 15 days program patients were advised to continue with the learned exercises during the next 6 months and no other advice or restrictions were provided.
Attendance at exercises and all notes are kept in a diary for each patient individually. During follow-up sessions, a questionnaire was filled out regarding how often exercises were performed at home (yes, no, how many times per week).


Range of motion improvement exercises:
- Passive stretching of the flexors and extensors of the toes and hallux was performed from a long sitting position, with knees extended and ankles in a neutral position. Flexion and extension of the toes and hallux are performed separately. Each stretching exercise is repeated 5 times, with each repetition held for 30 seconds.
- The self-stretching of the triceps surae was performed standing, with the contralateral limb positioned ahead, knee bent, and the ipsilateral limb positioned behind, with the foot facing forward. Each exercise position was repeated 5 times, with each repetition held for 30 seconds.
Approximate duration: 15-20 minutes.

Strengthening foot and ankle muscles exercises:
Muscle strengthening exercises for the toes' flexor muscles were performed from a supine lying position using manual resistance. Additionally, exercises for the intrinsic muscles of the foot involved sitting with the foot flat on the floor, gripping an object with the toes.
To strengthen the toes' extensor muscles, exercises were done from a supine lying position with manual resistance and from a sitting position with the foot flat, focusing on toe extension without allowing dorsiflexion.
Exercises for the flexors, extensors, invertors, and evertors of the foot and ankle were performed from a supine lying position using manual resistance. Standing on heels and toes was also included, performed for 1 set of 30 repetitions, except for standing on heels and toes which was done for 1 set of 20 repetitions.
Approximate duration:15 minutes.


Functional (Balance) Training:
- Standing on one leg with or without upper limb support, based on patient tolerance, performed 5 times for 30 seconds on each side.
- Standing on a rubber disc filled with air with support from both legs, performed 5 times for 30 seconds.
- Standing on heels and toes, performed 5 times for 30 seconds.
Balance training started with eyes open and progressed to eyes closed.
Approximate duration: 7 minutes.

Gait training:
- Walking over the heels, toes, lateral border, and medial border of feet at preferred speed.
- Walking in tandem.
- Walking with softening of heel and forefoot contact during normal walking.
- Walking while actively grabbing the floor with toes.
- Walking with normal foot rollover: heel strike, midfoot contact, lateral forefoot, medial forefoot, and hallux contact.
Execution: All walking tasks performed in a straight line at preferred speed for 60 meters each.
Approximate Duration: 10-15 minutes.
Intervention code [1] 328580 0
Treatment: Other
Intervention code [2] 328581 0
Rehabilitation
Comparator / control treatment
The patients in the control group received alpha-lipoic acid intravenously at a dose of 600 mg dissolved in 250 ml of 0.9% sodium chloride solution, administered over 60 minutes once a day for 15 consecutive therapy days, excluding weekends.
Control group
Active

Outcomes
Primary outcome [1] 338232 0
Any change in range of motion (ROM) in ankle joint.
Timepoint [1] 338232 0
Day 15 (primary outcome effect), 3 months and 6 months from baseline
Primary outcome [2] 338233 0
Any change in range of motion (ROM) in subtalar joint.
Timepoint [2] 338233 0
Day 15 (primary outcome effect), 3 months and 6 months from baseline
Primary outcome [3] 338609 0
Any change in range of motion (ROM) in first metatarsophalangeal joint.
Timepoint [3] 338609 0
Day 15 (primary outcome effect), 3 months and 6 months from baseline
Secondary outcome [1] 436595 0
Change in foot flexors muscle strength (Primary Outcome 4)
Timepoint [1] 436595 0
Day 15 (primary outcome effect), 3 months and 6 months from baseline
Secondary outcome [2] 436596 0
Change in foot extensors muscle strength (Primary Outcome 5)
Timepoint [2] 436596 0
Day 15 (primary outcome effect), 3 months and 6 months from baseline
Secondary outcome [3] 436597 0
Change in muscle strength of lower leg and foot muscles (Primary Outcome 6)
Timepoint [3] 436597 0
Day 15 (primary outcome effect), 3 months and 6 months from baseline
Secondary outcome [4] 436598 0
Sensation of hot
Timepoint [4] 436598 0
Day 15 (outcome effect), 3 months and 6 months from baseline.
Secondary outcome [5] 436599 0
Sensation of cold
Timepoint [5] 436599 0
Day 15 (outcome effect), 3 months and 6 months from baseline.
Secondary outcome [6] 436600 0
Gait performance - composite secondary outcome
Timepoint [6] 436600 0
Day 15 (outcome effect), 3 months and 6 months from baseline
Secondary outcome [7] 436601 0
Parameters of dynamic pressure distribution - composite secondary outcome
Timepoint [7] 436601 0
Day 15 (outcome effect), 3 months and 6 months from baseline
Secondary outcome [8] 436602 0
Contact time
Timepoint [8] 436602 0
Day 15 (outcome effect), 3 months and 6 months from baseline
Secondary outcome [9] 436603 0
Maximum force – composite secondary outcome
Timepoint [9] 436603 0
Day 15 (outcome effect), 3 months and 6 months from baseline
Secondary outcome [10] 436604 0
Time of maximum force - composite secondary outcome
Timepoint [10] 436604 0
Day 15 (outcome effect), 3 months and 6 months from baseline
Secondary outcome [11] 436605 0
Maximum pressure - composite secondary outcome
Timepoint [11] 436605 0
Day 15 (outcome effect), 3 months and 6 months from baseline

Eligibility
Key inclusion criteria
Inclusion criteria were as follows: age between 40 to 65 years, diabetes mellitus type 1 or 2 diagnosed for at least five years, stable glycemic control, body mass index ranging between 18,5 and 29,9 kg/m2 (normal and overweight), electroneurographic findings indicating presence of the diabetic neuropathy and ability to walk independently, without any device.
Minimum age
40 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unstable glycemic control, active diabetic foot ulcer, amputation, central neurological impairments, any other peripheral neurological impairments except diabetic polyneuropathy, orthopedic disease or previous surgery, rheumatology disease affecting movement, severe vestibular and ocular impairments that affect movement, severe nephropathy or diabetic polyneuropathy, presence of unresolved aetiology pain, intermittent claudication, ankle-brachial index value less than 0.8 or greater than 1.2 and presence of malignant disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A total of 90 sealed envelopes (45 with intervention and 45 with control group) was used for simple randomization of participants.
To ensure random allocation, an equal number of papers indicating group allocation were counted twice. These papers were then placed into envelopes, each securely sealed and checked to ensure the glue covered the entire surface. The envelopes were then mixed thoroughly on a table for several minutes. After mixing, each envelope was inspected again for any signs of tampering or detachment. Subsequently, the mixed envelopes were placed into a designated enrollment box.

When new participants met the enrollment criteria, envelopes were randomly drawn from the box for assignment. Opened envelopes were segregated into a separate container to prevent mixing with unopened ones. Upon opening the final envelope, all envelopes were meticulously counted and inspected for any discrepancies.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculation is based on difference between two means in independent samples t test. A sample size of 40 per group is sufficient to achieve 80% power to detect significant difference of 3.7 degrees change in ankle joint range of motion, between intervention and control group. Same sample size has 99% power to detect significant difference of muscle strenght change between groups.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
16/07/2021
Date of last participant enrolment
Anticipated
Actual
19/09/2022
Date of last data collection
Anticipated
Actual
3/04/2023
Sample size
Target
90
Accrual to date
Final
82
Recruitment outside Australia
Country [1] 26306 0
Bosnia and Herzegovina
State/province [1] 26306 0
Republika Srpska

Funding & Sponsors
Funding source category [1] 316509 0
Hospital
Name [1] 316509 0
Institute for Physical Medicine, Rehabilitation and Orthopedic Surgery “Dr Miroslav Zotovic” Banja Luka
Country [1] 316509 0
Bosnia and Herzegovina
Primary sponsor type
Hospital
Name
Institute for Physical Medicine, Rehabilitation and Orthopedic Surgery “Dr Miroslav Zotovic” Banja Luka
Address
Country
Bosnia and Herzegovina
Secondary sponsor category [1] 318688 0
None
Name [1] 318688 0
Address [1] 318688 0
Country [1] 318688 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315305 0
Ethics Committee of the Institute “Dr Miroslav Zotovic”
Ethics committee address [1] 315305 0
Ethics committee country [1] 315305 0
Bosnia and Herzegovina
Date submitted for ethics approval [1] 315305 0
24/02/2020
Approval date [1] 315305 0
05/03/2020
Ethics approval number [1] 315305 0
116-21-3090-1/20
Ethics committee name [2] 315307 0
Ethics Committee Faculty of Medicine, University of Banja Luka
Ethics committee address [2] 315307 0
Ethics committee country [2] 315307 0
Bosnia and Herzegovina
Date submitted for ethics approval [2] 315307 0
01/02/2020
Approval date [2] 315307 0
02/03/2020
Ethics approval number [2] 315307 0
18/4.3.13/20

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134282 0
Dr Snježana Novakovic Bursac
Address 134282 0
Institute for Physical Medicine, Rehabilitation and Orthopedic Surgery "Dr Miroslav Zotovic" Banja Luka/Slatinska Street No 11/City: Banja Luka/Postcode: 78000/State: Republika Srpska,
Country 134282 0
Bosnia and Herzegovina
Phone 134282 0
+387 65 618789
Fax 134282 0
Email 134282 0
[email protected]
Contact person for public queries
Name 134283 0
Snježana Novakovic Bursac
Address 134283 0
Institute for Physical Medicine, Rehabilitation and Orthopedic Surgery "Dr Miroslav Zotovic" Banja Luka/Slatinska Street No 11/City: Banja Luka/Postcode: 78000/State: Republika Srpska,
Country 134283 0
Bosnia and Herzegovina
Phone 134283 0
+387 65 618789
Fax 134283 0
Email 134283 0
[email protected]
Contact person for scientific queries
Name 134284 0
Snježana Novakovic Bursac
Address 134284 0
Institute for Physical Medicine, Rehabilitation and Orthopedic Surgery "Dr Miroslav Zotovic" Banja Luka/Slatinska Street No 11/City: Banja Luka/Postcode: 78000/State: Republika Srpska,
Country 134284 0
Bosnia and Herzegovina
Phone 134284 0
+387 65 618789
Fax 134284 0
Email 134284 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The individual data of participants are not essential for the results of the study. During the process of obtaining consent for participation in the study, we committed to ensuring that the data of individual participants in the study would remain protected


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.