Depression DisordersTNF; IL-6NCT06775548
Comparing the Effects of Aerobic & Resistance Exercises and Vitamins D & E on Oxidative Stress & Inflammatory Markers Among Patients with Depression
A study testing Aerobic Exercises + Vitamin E, Resistance Exercises + Vitamin E and Aerobic Exercises + Vitamin D in people with Depression Disorders, run by Ziauddin University at 1 site in Pakistan.
Trial summary
Depression has been ranked as the fourth leading contributor to disability globally. As per data provided by the World Health Organization (WHO), depression affects approximately 3.8% of the global population, constituting approximately 280 million individuals worldwide, with an annual suicide-related mortality of… Read more about this study
- Who is it for?
- Ages 25 to 35 years
- Conditions the study is for
- Depression Disorders
- What is being tested?
- Aerobic Exercises + Vitamin E, Resistance Exercises + Vitamin E and Aerobic Exercises + Vitamin D
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 1 sitePakistan
- Study dates
- 2 Sep 2024to 5 Aug 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosed patients with mild to moderate depression, aged between 25-35 years referred by Psychiatrist with no other Psychiatric disease attending the respective unit of Creek General Hospital and Dr. Ziauddin Hospital. (Kivani M et al, 2022, Khan B et al., 2022).
- Individuals both with and without current psychoactive medication (such as antidepressants or anxiolytics) will be enrolled. (O'Sullivan et al., 2023)
- Participants willing to participate to the intervention.
Who cannot join
- Participants with diagnosed cardiovascular diseases,
- Participants with pregnant women,
- Participants with use of beta-blockers,
- Participants with a history of severe mental illnesses (mentally handicapped),
- Participants with hypertension, hyperparathyroidism,
- Participants with current significant substance or alcohol abuse, ongoing burn-out syndrome, and
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- Participants with An elevated suicide risk determined by the Psychiatrist.
- Participants with Prisoners
- Participants with chronic diseases such as liver and renal diseases, mal-absorption syndrome, and other diseases that can affect the level of vitamin D.
- Patients with physical limitations that would prohibit the participation in following exercise protocol.
- Participants consuming dietary supplements two months prior to the intervention.
- Participation in regular exercise during the past 6 months (2 days/week).
- Non cooperative patients and refused to continue the intervention program.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effects of Exercises and Vitamins on Oxidative Stress & Inflammatory Markers Among Patients with Depression
Depression has been ranked as the fourth leading contributor to disability globally. As per data provided by the World Health Organization (WHO), depression affects approximately 3.8% of the global population, constituting approximately 280 million individuals worldwide, with an annual suicide-related mortality of 700,000 people GHDx 2023). Women are 50% more affected with depression as compared to men. Approximately 27.4% have experienced symptoms associated with anxiety and depression in Pakistan. The increasing prevalence and yearly occurrence influenced by the COVID-19 have compelled us to reevaluate the significance of mental well-being. Furthermore, based on the latest data, there has been an increase of 53.2 million cases of depressive disorder worldwide, indicating a growth of 27.6% throughout this pandemic. The prevalence of depression is uniform in both developed and economically challenged nations, independent of cultural background, origin, or ethnicity. Depression has various forms which include major depressive disorder (MDD), bipolar disorder (manic depression), persistent depressive disorder (dysthymia), and seasonal affective disorder (SAD). In the present time, MDD is the leading cause of global disability, contributing to 7.5% of years lived with a disability. (YLD) worldwide, with an estimated annual cost surpassing $US 1 trillion.
The primary etiology of MDD is disturbances in neurotransmitters and neuroendocrine regulation, accompanied by a complex interaction of genetic and environmental factors. In addition to these factors, increasing attention has been directed towards understanding the pathophysiology of MDD through the relationship between oxidative stress and inflammation. Essential enzymatic antioxidants, particularly Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD), play a crucial role in moderating oxidative stress. Oxidative stress arises from an imbalance between the generation of reactive oxygen species (ROS) and the body's capacity to counteract them. Studies indicate a tendency for reduced GPx and SOD activity in individuals with MDD, leading to heightened oxidative stress.
Read more
Furthermore, the involvement of pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF) and Interleukin-6 (IL-6), in the inflammatory processes associated with depression is noteworthy. Persistent inflammation is associated with the activation of the kynurenine pathway, triggering the production of neurotoxic metabolites that may contribute to observed neurobiological changes in MDD. Elevated levels of TNF and IL-6, key immune response mediators, are observed in individuals with depression. These cytokines influence neurotransmitter metabolism, disrupt the blood-brain barrier, and activate microglia, spreading neuro-inflammation. The bidirectional interplay between oxidative stress and inflammation establishes a cyclically reinforcing paradigm, amplifying the neurobiological substrates of depression.. Moreover, deficiencies in various vitamins and minerals are significantly associated with Major Depressive Disorder (MDD), including vitamin D and E. Vitamin D and its metabolite calcitriol may act as a defense mechanism for the brain, guarding against the depletion of dopamine and serotonin whereas vitamin E has an antidepressant-like effect.
The management of major depressive disorder encompasses diverse treatment approaches, comprising pharmacological, psychotherapeutic, interventional, and lifestyle modifications, such as incorporating exercise and dietary changes. While the current antidepressants are more effective than placebos in adults with MDD, limitations of antidepressant treatment include a prolonged therapeutic time lag required for the clinical betterment of depressive symptoms and various side effects linked to their usage. These side effects frequently lead to treatment discontinuation by patients. Consequently, adjunctive treatments may play a crucial role in managing this disorder, particularly in cases of treatment resistance.
Engaging in regular exercise exerts a beneficial impact on symptoms commonly associated with depression. The consistent practice of physical activity positively influences various physiological aspects, encompassing neurotransmitter levels, neurotrophic factors, hormonal balance, immune modulation, sleep quality, and cognitive functions. This comprehensive influence collectively provides substantial evidence for the therapeutic effectiveness of exercise in alleviating depressive symptoms. Hence, the objective of the current study is to investigate the outcomes of aerobic and resistance exercises in conjunction with vitamin supplementation on individuals diagnosed with Major Depressive Disorder (MDD).
Read the detailed description
A total number of 116 participants will be recruited in the study. After the voluntarily consent, all the participants will be equally divided into four of the treatment group Group-A, B, C and D using envelop method of simple random sampling technique. In addition, a total of 116 sealed envelopes, comprises of 29 envelopes for each group will be presented to the patients. Each patient will be asked to select one envelope of their choice. Upon selection of the envelope, patients will be allocated to the respective group. Thus, each group will comprise of 29 participants Afterwards, pre-assessment will be performed for each patient on all 3 outcome measures i.e. Oxidative stress (SOD \& GPX), inflammatory markers (TNF alpha \& IL-6) Depression severity (PHQ-9) respectively.
Participants in Group-A will be receiving Aerobic Exercise with Vitamin E, Group-B participants will be receiving Resistance Exercise with Vitamin E, Group C: Aerobic Exercise with Vitamin D, while Group D will be receiving Resistance Exercise with Vitamin D. Whereas, all the groups will be given 48 sessions of their respective protocol, comprising of 30 minutes, 4 times/week for the duration of 12 weeks.
Participants referred to the study will undergo a thorough screening process as discussed below to determine their eligibility.
The recruitment of patients will be conducted by a psychiatrist, adhering to predefined inclusion and exclusion criteria. Patients will undergo screening and be categorized as having Major Depressive Disorder (MDD) if they exhibit at least one of the two primary criteria-depressed mood or anhedonia (the inability to experience pleasure or loss of interest)-along with four or more secondary symptoms persisting for a minimum period of 2 weeks, as per DSM-5 guidelines (American Psychiatric Association, 2013).
They will then be screened through PARQ \& YOU questionnaire by physical therapist. Subsequently, the investigator will provide a comprehensive overview of the study to the patients and secure informed consent upon their agreement. Demographic information and pertinent variables, including the duration of the disease and comorbidities, will be documented before the baseline assessment. All patients will adhere to their routine pharmacological care throughout the intervention period.
An orientation session will be arranged before starting the intervention in which the physical therapists in detailed will brief the participants regarding the protocol. The intervention will last for duration of 12 weeks with a total of 48 sessions. First, the participant will perform 1 week of training as part of familiarization phase.
- Conditions
- Depression Disorders
- Being tested
- Aerobic Exercises + Vitamin E, Resistance Exercises + Vitamin E, Aerobic Exercises + Vitamin D, Resistance Exercises + Vitamin D
- Keywords
- Depression, Oxidative Stress, Inflammatory Markers, Aerobic Exercises, Resistance Exercises, Vitamin E, Vitamin D
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aerobic Exercises + Vitamin EOther
For aerobic exercise, patient will perform cycling. The patient will perform stationary bike with an intensity of 60-85% of MHR by using Karvonean formula for duration of 30 minutes for 4 days/ week. Participants will be advised by the physical therapist to sit on a cycle ergometer with back supported, hands holding the handle bar and feet firmly placed on the pedals.
The imprint of FITT protcol by ACSM for aerobic exercise will be as follows, Frequency: 4 days/week Intensity: 60-85% of MHR Time: 30 minutes Type: Stationary bike
Resistance Exercises + Vitamin EOther
The strength training protocol will focus on 10 major muscles of the body. The sessions will be performed for 4 days per week, lasting approximately 30 minutes. The training will be divided in a systematical manner, on first- and third-day participant will perform strength training of upper limb and abdominal muscles that include: Biceps, Triceps, Pectoralis Major, Deltoid, and abdominal muscles. On second and fourth day, participant will perform strength training of lower back and lower limb muscles that include: Latissimus Dorsi, Abdominals, Back Extensors, Hamstrings, Quadriceps and Calf. The intensity of the weight bearing exercises will be calculated using 1 Repetition Maximum (RM) method. The protocol will be divided as follows: 2 days the participant will perform exercises for upper limb and 2 days, patient will perform exercises for lower limb.
Aerobic Exercises + Vitamin DOther
For aerobic exercise, patient will perform cycling. The patient will perform stationary bike with an intensity of 60-85% of MHR by using Karvonean formula for duration of 30 minutes for 4 days/ week. Participants will be advised by the physical therapist to sit on a cycle ergometer with back supported, hands holding the handle bar and feet firmly placed on the pedals. The imprint of FITT protcol by ACSM for aerobic exercise will be as follows, Frequency: 4 days/week Intensity: 60-85% of MHR Time: 30 minutes Type: Stationary bike
Resistance Exercises + Vitamin DOther
The strength training protocol will focus on 10 major muscles of the body. The sessions will be performed for 4 days per week, lasting approximately 30 minutes. The training will be divided in a systematical manner, on first- and third-day participant will perform strength training of upper limb and abdominal muscles that include: Biceps, Triceps, Pectoralis Major, Deltoid, and abdominal muscles. On second and fourth day, participant will perform strength training of lower back and lower limb muscles that include: Latissimus Dorsi, Abdominals, Back Extensors, Hamstrings, Quadriceps and Calf. The intensity of the weight bearing exercises will be calculated using 1 Repetition Maximum (RM) method. The protocol will be divided as follows: 2 days the participant will perform exercises for upper limb and 2 days, patient will perform exercises for lower limb.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Aerobic Exercises with Vitamin E Receives: Other: Aerobic Exercises + Vitamin E |
| Group B | Experimental | Resistance Exercises with Vitamin E Receives: Other: Resistance Exercises + Vitamin E |
| Group C | Experimental | Aerobic Exercises with Vitamin D Receives: Other: Aerobic Exercises + Vitamin D |
| Group D | Experimental | Resistance Exercises with Vitamin D Receives: Other: Resistance Exercises + Vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glutathione Peroxidase and Superoxide Dismutase
Oxidative stress will be assessed in each group using a colorimetric method and commercially available kits. This method involves measuring the optical density at 560 nm of the blue formazan dye produced during the interaction of nitro blue tetrazolium with superoxide radicals generated through the use of xanthine and xanthine oxidase. The Superoxide Dismutase present in the sample works to neutralize the superoxide radicals in the medium, thereby inhibiting the formazan reaction. Specifically, one unit of SOD reduces the nitro blue tetrazolium at a rate of 50% under the specified assay conditions
Measured: Baseline
Glutathione Peroxidase and Superoxide Dismutase
Oxidative stress will be assessed in each group using a colorimetric method and commercially available kits. This method involves measuring the optical density at 560 nm of the blue formazan dye produced during the interaction of nitro blue tetrazolium with superoxide radicals generated through the use of xanthine and xanthine oxidase. The Superoxide Dismutase present in the sample works to neutralize the superoxide radicals in the medium, thereby inhibiting the formazan reaction. Specifically, one unit of SOD reduces the nitro blue tetrazolium at a rate of 50% under the specified assay conditions
Measured: 12 weeks
Inflammatory Markers
TNF and IL-6 will be assessed using commercially available ELISA kits. The procedures for preparing reagents, standards, and serum samples, as well as the overall assay process, will be conducted in accordance with the manufacturer's instructions for each respective ELISA kit. Each ELISA kit plate consisted of 116 microtiter wells, all of which will be coated with antibodies targeting a specific antigenic site of the respective cytokine molecule. The concentrations of IL-6 and TNF will be reported in units of pg/mL and mg/L, respectively
Measured: Baseline
Inflammatory Markers
TNF and IL-6 will be assessed using commercially available ELISA kits. The procedures for preparing reagents, standards, and serum samples, as well as the overall assay process, will be conducted in accordance with the manufacturer's instructions for each respective ELISA kit. Each ELISA kit plate consisted of 116 microtiter wells, all of which will be coated with antibodies targeting a specific antigenic site of the respective cytokine molecule. The concentrations of IL-6 and TNF will be reported in units of pg/mL and mg/L, respectively
Measured: 12 weeks
Patient Health Questionnaire (PHQ-9)
PHQ- 9 is a subjective score for assessing depression severity level. It has 9 questions with a maximum score of 27.
Measured: Baseline
Patient Health Questionnaire (PHQ-9)
PHQ- 9 is a subjective score for assessing depression severity level. It has 9 questions with a maximum score of 27.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2025
- Study start2 Sep 2024
- Primary completion5 Aug 2025 (estimated)
- Study completion5 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (31)Papers the sponsor has linked to this study.
- Other trials for Depression DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ziauddin University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erum Tanveer, Ziauddin University
- Investigators
- Erum Tanveer, Principal investigator, Ziauddin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06775548
- Sponsor's protocol ID
- 86404243ETREH
- Acronym
- TNF; IL-6
- Status last verified
- Jan 2025
- First submitted
- 9 Jan 2025
- Last updated
- 15 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sun Y, Fu Z, Bo Q, Mao Z, Ma X, Wang C. The reliability and validity of PHQ-9 in patients with major depressive disorder in psychiatric hospital. BMC Psychiatry. 2020 Sep 29;20(1):474. doi: 10.1186/s12888-020-02885-6.
PubMed 32993604Schuch FB, Deslandes AC, Stubbs B, Gosmann NP, Silva CT, Fleck MP. Neurobiological effects of exercise on major depressive disorder: A systematic review. Neurosci Biobehav Rev. 2016 Feb;61:1-11. doi: 10.1016/j.neubiorev.2015.11.012. Epub 2015 Dec 2.
PubMed 26657969COVID-19 Mental Disorders Collaborators. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021 Nov 6;398(10312):1700-1712. doi: 10.1016/S0140-6736(21)02143-7. Epub 2021 Oct 8.
PubMed 34634250Ross RE, VanDerwerker CJ, Saladin ME, Gregory CM. The role of exercise in the treatment of depression: biological underpinnings and clinical outcomes. Mol Psychiatry. 2023 Jan;28(1):298-328. doi: 10.1038/s41380-022-01819-w. Epub 2022 Oct 17.
PubMed 36253441Palapar L, Kerse N, Rolleston A, den Elzen WPJ, Gussekloo J, Blom JW, Robinson L, Martin-Ruiz C, Duncan R, Arai Y, Takayama M, Teh R; TULIP Consortium. Anaemia and physical and mental health in the very old: An individual participant data meta-analysis of four longitudinal studies of ageing. Age Ageing. 2021 Jan 8;50(1):113-119. doi: 10.1093/ageing/afaa178.
PubMed 32939533O'Sullivan D, Gordon BR, Lyons M, Meyer JD, Herring MP. Effects of resistance exercise training on depressive symptoms among young adults: A randomized controlled trial. Psychiatry Res. 2023 Aug;326:115322. doi: 10.1016/j.psychres.2023.115322. Epub 2023 Jun 28.
PubMed 37429171Nishuty NL, Khandoker MMH, Karmoker JR, Ferdous S, Shahriar M, Qusar MMAS, Islam MS, Kadir MF, Islam MR. Evaluation of Serum Interleukin-6 and C-reactive Protein Levels in Drug-naive Major Depressive Disorder Patients. Cureus. 2019 Jan 11;11(1):e3868. doi: 10.7759/cureus.3868.
PubMed 30899619Moraes HS, Silveira HS, Oliveira NA, Matta Mello Portugal E, Araujo NB, Vasques PE, Bergland A, Santos TM, Engedal K, Coutinho ES, Schuch FB, Laks J, Deslandes AC. Is Strength Training as Effective as Aerobic Training for Depression in Older Adults? A Randomized Controlled Trial. Neuropsychobiology. 2020;79(2):141-149. doi: 10.1159/000503750. Epub 2019 Oct 28.
PubMed 31658460Mikola T, Marx W, Lane MM, Hockey M, Loughman A, Rajapolvi S, Rocks T, O'Neil A, Mischoulon D, Valkonen-Korhonen M, Lehto SM, Ruusunen A. The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2023 Nov;63(33):11784-11801. doi: 10.1080/10408398.2022.2096560. Epub 2022 Jul 11.
PubMed 35816192Mandolesi L, Polverino A, Montuori S, Foti F, Ferraioli G, Sorrentino P, Sorrentino G. Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits. Front Psychol. 2018 Apr 27;9:509. doi: 10.3389/fpsyg.2018.00509. eCollection 2018.
PubMed 29755380Maurus I, Hasan A, Roh A, Takahashi S, Rauchmann B, Keeser D, Malchow B, Schmitt A, Falkai P. Neurobiological effects of aerobic exercise, with a focus on patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2019 Aug;269(5):499-515. doi: 10.1007/s00406-019-01025-w. Epub 2019 May 21.
PubMed 31115660Li J, Wang L, Wang Z, Zhao F, Sun Y, Lu Y, Yang L. Association between suicide attempts and anemia in late-life depression inpatients. BMC Geriatr. 2024 Jan 10;24(1):43. doi: 10.1186/s12877-023-04649-9.
PubMed 38200429Jamilian M, Shojaei A, Samimi M, Afshar Ebrahimi F, Aghadavod E, Karamali M, Taghizadeh M, Jamilian H, Alaeinasab S, Jafarnejad S, Asemi Z. The effects of omega-3 and vitamin E co-supplementation on parameters of mental health and gene expression related to insulin and inflammation in subjects with polycystic ovary syndrome. J Affect Disord. 2018 Mar 15;229:41-47. doi: 10.1016/j.jad.2017.12.049. Epub 2017 Dec 28.
PubMed 29306057Imboden C, Gerber M, Beck J, Eckert A, Lejri I, Puhse U, Holsboer-Trachsler E, Hatzinger M. Aerobic Exercise and Stretching as Add-On to Inpatient Treatment for Depression Have No Differential Effects on Stress-Axis Activity, Serum-BDNF, TNF-Alpha and Objective Sleep Measures. Brain Sci. 2021 Mar 24;11(4):411. doi: 10.3390/brainsci11040411.
PubMed 33805073Nedic Erjavec G, Sagud M, Nikolac Perkovic M, Svob Strac D, Konjevod M, Tudor L, Uzun S, Pivac N. Depression: Biological markers and treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 8;105:110139. doi: 10.1016/j.pnpbp.2020.110139. Epub 2020 Oct 15.
PubMed 33068682
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Exercises and Vitamins on Oxidative Stress & Inflammatory Markers Among Patients with Depression
- ClinicalTrials.gov ID
- NCT06775548
- Acronym / sponsor ID
- TNF; IL-6 / 86404243ETREH
- Conditions
- Depression Disorders
- Keywords
- Depression, Oxidative Stress, Inflammatory Markers, Aerobic Exercises, Resistance Exercises, Vitamin E, Vitamin D
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 116 participants (estimated)
- Lead sponsor
- Ziauddin UniversityUniversity, hospital or other
- Study start
- 2 Sep 2024 (actual)
- Primary completion
- 5 Aug 2025 (estimated)
- Study completion
- 5 Aug 2025 (estimated)
- First posted
- 15 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Depression has been ranked as the fourth leading contributor to disability globally. As per data provided by the World Health Organization (WHO), depression affects approximately 3.8% of the global population, constituting approximately 280 million individuals worldwide, with an annual suicide-related mortality of 700,000 people GHDx 2023). Women are 50% more affected with depression as compared to men. Approximately 27.4% have experienced symptoms associated with anxiety and depression in Pakistan. The increasing prevalence and yearly occurrence influenced by the COVID-19 have compelled us to reevaluate the significance of mental well-being. Furthermore, based on the latest data, there has been an increase of 53.2 million cases of depressive disorder worldwide, indicating a growth of 27.6% throughout this pandemic. The prevalence of depression is uniform in both developed and economically challenged nations, independent of cultural background, origin, or ethnicity. Depression has various forms which include major depressive disorder (MDD), bipolar disorder (manic depression), persistent depressive disorder (dysthymia), and seasonal affective disorder (SAD). In the present time, MDD is the leading cause of global disability, contributing to 7.5% of years lived with a disability. (YLD) worldwide, with an estimated annual cost surpassing $US 1 trillion.
The primary etiology of MDD is disturbances in neurotransmitters and neuroendocrine regulation, accompanied by a complex interaction of genetic and environmental factors. In addition to these factors, increasing attention has been directed towards understanding the pathophysiology of MDD through the relationship between oxidative stress and inflammation. Essential enzymatic antioxidants, particularly Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD), play a crucial role in moderating oxidative stress. Oxidative stress arises from an imbalance between the generation of reactive oxygen species (ROS) and the body's capacity to counteract them. Studies indicate a tendency for reduced GPx and SOD activity in individuals with MDD, leading to heightened oxidative stress.
Furthermore, the involvement of pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF) and Interleukin-6 (IL-6), in the inflammatory processes associated with depression is noteworthy. Persistent inflammation is associated with the activation of the kynurenine pathway, triggering the production of neurotoxic metabolites that may contribute to observed neurobiological changes in MDD. Elevated levels of TNF and IL-6, key immune response mediators, are observed in individuals with depression. These cytokines influence neurotransmitter metabolism, disrupt the blood-brain barrier, and activate microglia, spreading neuro-inflammation. The bidirectional interplay between oxidative stress and inflammation establishes a cyclically reinforcing paradigm, amplifying the neurobiological substrates of depression.. Moreover, deficiencies in various vitamins and minerals are significantly associated with Major Depressive Disorder (MDD), including vitamin D and E. Vitamin D and its metabolite calcitriol may act as a defense mechanism for the brain, guarding against the depletion of dopamine and serotonin whereas vitamin E has an antidepressant-like effect.
The management of major depressive disorder encompasses diverse treatment approaches, comprising pharmacological, psychotherapeutic, interventional, and lifestyle modifications, such as incorporating exercise and dietary changes. While the current antidepressants are more effective than placebos in adults with MDD, limitations of antidepressant treatment include a prolonged therapeutic time lag required for the clinical betterment of depressive symptoms and various side effects linked to their usage. These side effects frequently lead to treatment discontinuation by patients. Consequently, adjunctive treatments may play a crucial role in managing this disorder, particularly in cases of treatment resistance.
Engaging in regular exercise exerts a beneficial impact on symptoms commonly associated with depression. The consistent practice of physical activity positively influences various physiological aspects, encompassing neurotransmitter levels, neurotrophic factors, hormonal balance, immune modulation, sleep quality, and cognitive functions. This comprehensive influence collectively provides substantial evidence for the therapeutic effectiveness of exercise in alleviating depressive symptoms. Hence, the objective of the current study is to investigate the outcomes of aerobic and resistance exercises in conjunction with vitamin supplementation on individuals diagnosed with Major Depressive Disorder (MDD).
Detailed description
A total number of 116 participants will be recruited in the study. After the voluntarily consent, all the participants will be equally divided into four of the treatment group Group-A, B, C and D using envelop method of simple random sampling technique. In addition, a total of 116 sealed envelopes, comprises of 29 envelopes for each group will be presented to the patients. Each patient will be asked to select one envelope of their choice. Upon selection of the envelope, patients will be allocated to the respective group. Thus, each group will comprise of 29 participants Afterwards, pre-assessment will be performed for each patient on all 3 outcome measures i.e. Oxidative stress (SOD \& GPX), inflammatory markers (TNF alpha \& IL-6) Depression severity (PHQ-9) respectively.
Participants in Group-A will be receiving Aerobic Exercise with Vitamin E, Group-B participants will be receiving Resistance Exercise with Vitamin E, Group C: Aerobic Exercise with Vitamin D, while Group D will be receiving Resistance Exercise with Vitamin D. Whereas, all the groups will be given 48 sessions of their respective protocol, comprising of 30 minutes, 4 times/week for the duration of 12 weeks.
Participants referred to the study will undergo a thorough screening process as discussed below to determine their eligibility.
The recruitment of patients will be conducted by a psychiatrist, adhering to predefined inclusion and exclusion criteria. Patients will undergo screening and be categorized as having Major Depressive Disorder (MDD) if they exhibit at least one of the two primary criteria-depressed mood or anhedonia (the inability to experience pleasure or loss of interest)-along with four or more secondary symptoms persisting for a minimum period of 2 weeks, as per DSM-5 guidelines (American Psychiatric Association, 2013).
They will then be screened through PARQ \& YOU questionnaire by physical therapist. Subsequently, the investigator will provide a comprehensive overview of the study to the patients and secure informed consent upon their agreement. Demographic information and pertinent variables, including the duration of the disease and comorbidities, will be documented before the baseline assessment. All patients will adhere to their routine pharmacological care throughout the intervention period.
An orientation session will be arranged before starting the intervention in which the physical therapists in detailed will brief the participants regarding the protocol. The intervention will last for duration of 12 weeks with a total of 48 sessions. First, the participant will perform 1 week of training as part of familiarization phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Other: Aerobic Exercises + Vitamin EAerobic Exercises with Vitamin E |
| Group B | Experimental | Other: Resistance Exercises + Vitamin EResistance Exercises with Vitamin E |
| Group C | Experimental | Other: Aerobic Exercises + Vitamin DAerobic Exercises with Vitamin D |
| Group D | Experimental | Other: Resistance Exercises + Vitamin DResistance Exercises with Vitamin D |
Who may qualify
- Ages
- 25 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Diagnosed patients with mild to moderate depression, aged between 25-35 years referred by Psychiatrist with no other Psychiatric disease attending the respective unit of Creek General Hospital and Dr. Ziauddin Hospital. (Kivani M et al, 2022, Khan B et al., 2022).
- Individuals both with and without current psychoactive medication (such as antidepressants or anxiolytics) will be enrolled. (O'Sullivan et al., 2023)
- Participants willing to participate to the intervention.
Key exclusion criteria (13 listed)
- Participants with diagnosed cardiovascular diseases,
- Participants with pregnant women,
- Participants with use of beta-blockers,
- Participants with a history of severe mental illnesses (mentally handicapped),
- Participants with hypertension, hyperparathyroidism,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aerobic Exercises + Vitamin EFor aerobic exercise, patient will perform cycling. The patient will perform stationary bike with an intensity of 60-85% of MHR by using Karvonean formula for duration of 30 minutes for 4 days/ week. Participants will be advised by the physical therapist to sit on a cycle ergometer with back supported, hands holding the handle bar and feet firmly placed on the pedals. The imprint of FITT protcol by ACSM for aerobic exercise will be as follows, Frequency: 4 days/week Intensity: 60-85% of MHR Time: 30 minutes Type: Stationary bike | Other | Group A |
| Resistance Exercises + Vitamin EThe strength training protocol will focus on 10 major muscles of the body. The sessions will be performed for 4 days per week, lasting approximately 30 minutes. The training will be divided in a systematical manner, on first- and third-day participant will perform strength training of upper limb and abdominal muscles that include: Biceps, Triceps, Pectoralis Major, Deltoid, and abdominal muscles. On second and fourth day, participant will perform strength training of lower back and lower limb muscles that include: Latissimus Dorsi, Abdominals, Back Extensors, Hamstrings, Quadriceps and Calf. The intensity of the weight bearing exercises will be calculated using 1 Repetition Maximum (RM) method. The protocol will be divided as follows: 2 days the participant will perform exercises for upper limb and 2 days, patient will perform exercises for lower limb. | Other | Group B |
| Aerobic Exercises + Vitamin DFor aerobic exercise, patient will perform cycling. The patient will perform stationary bike with an intensity of 60-85% of MHR by using Karvonean formula for duration of 30 minutes for 4 days/ week. Participants will be advised by the physical therapist to sit on a cycle ergometer with back supported, hands holding the handle bar and feet firmly placed on the pedals. The imprint of FITT protcol by ACSM for aerobic exercise will be as follows, Frequency: 4 days/week Intensity: 60-85% of MHR Time: 30 minutes Type: Stationary bike | Other | Group C |
| Resistance Exercises + Vitamin DThe strength training protocol will focus on 10 major muscles of the body. The sessions will be performed for 4 days per week, lasting approximately 30 minutes. The training will be divided in a systematical manner, on first- and third-day participant will perform strength training of upper limb and abdominal muscles that include: Biceps, Triceps, Pectoralis Major, Deltoid, and abdominal muscles. On second and fourth day, participant will perform strength training of lower back and lower limb muscles that include: Latissimus Dorsi, Abdominals, Back Extensors, Hamstrings, Quadriceps and Calf. The intensity of the weight bearing exercises will be calculated using 1 Repetition Maximum (RM) method. The protocol will be divided as follows: 2 days the participant will perform exercises for upper limb and 2 days, patient will perform exercises for lower limb. | Other | Group D |
Primary outcome
Glutathione Peroxidase and Superoxide Dismutase
Time frame: Baseline
Oxidative stress will be assessed in each group using a colorimetric method and commercially available kits. This method involves measuring the optical density at 560 nm of the blue formazan dye produced during the interaction of nitro blue tetrazolium with superoxide radicals generated through the use of xanthine and xanthine oxidase. The Superoxide Dismutase present in the sample works to neutralize the superoxide radicals in the medium, thereby inhibiting the formazan reaction. Specifically, one unit of SOD reduces the nitro blue tetrazolium at a rate of 50% under the specified assay conditions
Glutathione Peroxidase and Superoxide Dismutase
Time frame: 12 weeks
Oxidative stress will be assessed in each group using a colorimetric method and commercially available kits. This method involves measuring the optical density at 560 nm of the blue formazan dye produced during the interaction of nitro blue tetrazolium with superoxide radicals generated through the use of xanthine and xanthine oxidase. The Superoxide Dismutase present in the sample works to neutralize the superoxide radicals in the medium, thereby inhibiting the formazan reaction. Specifically, one unit of SOD reduces the nitro blue tetrazolium at a rate of 50% under the specified assay conditions
Inflammatory Markers
Time frame: Baseline
TNF and IL-6 will be assessed using commercially available ELISA kits. The procedures for preparing reagents, standards, and serum samples, as well as the overall assay process, will be conducted in accordance with the manufacturer's instructions for each respective ELISA kit. Each ELISA kit plate consisted of 116 microtiter wells, all of which will be coated with antibodies targeting a specific antigenic site of the respective cytokine molecule. The concentrations of IL-6 and TNF will be reported in units of pg/mL and mg/L, respectively
Inflammatory Markers
Time frame: 12 weeks
TNF and IL-6 will be assessed using commercially available ELISA kits. The procedures for preparing reagents, standards, and serum samples, as well as the overall assay process, will be conducted in accordance with the manufacturer's instructions for each respective ELISA kit. Each ELISA kit plate consisted of 116 microtiter wells, all of which will be coated with antibodies targeting a specific antigenic site of the respective cytokine molecule. The concentrations of IL-6 and TNF will be reported in units of pg/mL and mg/L, respectively
Patient Health Questionnaire (PHQ-9)
Time frame: Baseline
PHQ- 9 is a subjective score for assessing depression severity level. It has 9 questions with a maximum score of 27.
Patient Health Questionnaire (PHQ-9)
Time frame: 12 weeks
PHQ- 9 is a subjective score for assessing depression severity level. It has 9 questions with a maximum score of 27.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2025.
- Background: PubMed 32993604Sun Y, Fu Z, Bo Q, Mao Z, Ma X, Wang C. The reliability and validity of PHQ-9 in patients with major depressive disorder in psychiatric hospital. BMC Psychiatry. 2020 Sep 29;20(1):474. doi: 10.1186/s12888-020-02885-6.
- Background: PubMed 26657969Schuch FB, Deslandes AC, Stubbs B, Gosmann NP, Silva CT, Fleck MP. Neurobiological effects of exercise on major depressive disorder: A systematic review. Neurosci Biobehav Rev. 2016 Feb;61:1-11. doi: 10.1016/j.neubiorev.2015.11.012. Epub 2015 Dec 2.
- Background: PubMed 34634250COVID-19 Mental Disorders Collaborators. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021 Nov 6;398(10312):1700-1712. doi: 10.1016/S0140-6736(21)02143-7. Epub 2021 Oct 8.
- Background: PubMed 36253441Ross RE, VanDerwerker CJ, Saladin ME, Gregory CM. The role of exercise in the treatment of depression: biological underpinnings and clinical outcomes. Mol Psychiatry. 2023 Jan;28(1):298-328. doi: 10.1038/s41380-022-01819-w. Epub 2022 Oct 17.
- Background: PubMed 32939533Palapar L, Kerse N, Rolleston A, den Elzen WPJ, Gussekloo J, Blom JW, Robinson L, Martin-Ruiz C, Duncan R, Arai Y, Takayama M, Teh R; TULIP Consortium. Anaemia and physical and mental health in the very old: An individual participant data meta-analysis of four longitudinal studies of ageing. Age Ageing. 2021 Jan 8;50(1):113-119. doi: 10.1093/ageing/afaa178.
- Background: PubMed 37429171O'Sullivan D, Gordon BR, Lyons M, Meyer JD, Herring MP. Effects of resistance exercise training on depressive symptoms among young adults: A randomized controlled trial. Psychiatry Res. 2023 Aug;326:115322. doi: 10.1016/j.psychres.2023.115322. Epub 2023 Jun 28.
- Background: PubMed 30899619Nishuty NL, Khandoker MMH, Karmoker JR, Ferdous S, Shahriar M, Qusar MMAS, Islam MS, Kadir MF, Islam MR. Evaluation of Serum Interleukin-6 and C-reactive Protein Levels in Drug-naive Major Depressive Disorder Patients. Cureus. 2019 Jan 11;11(1):e3868. doi: 10.7759/cureus.3868.
- Background: PubMed 31658460Moraes HS, Silveira HS, Oliveira NA, Matta Mello Portugal E, Araujo NB, Vasques PE, Bergland A, Santos TM, Engedal K, Coutinho ES, Schuch FB, Laks J, Deslandes AC. Is Strength Training as Effective as Aerobic Training for Depression in Older Adults? A Randomized Controlled Trial. Neuropsychobiology. 2020;79(2):141-149. doi: 10.1159/000503750. Epub 2019 Oct 28.
- Background: PubMed 35816192Mikola T, Marx W, Lane MM, Hockey M, Loughman A, Rajapolvi S, Rocks T, O'Neil A, Mischoulon D, Valkonen-Korhonen M, Lehto SM, Ruusunen A. The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2023 Nov;63(33):11784-11801. doi: 10.1080/10408398.2022.2096560. Epub 2022 Jul 11.
- Background: PubMed 29755380Mandolesi L, Polverino A, Montuori S, Foti F, Ferraioli G, Sorrentino P, Sorrentino G. Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits. Front Psychol. 2018 Apr 27;9:509. doi: 10.3389/fpsyg.2018.00509. eCollection 2018.
- Background: PubMed 31115660Maurus I, Hasan A, Roh A, Takahashi S, Rauchmann B, Keeser D, Malchow B, Schmitt A, Falkai P. Neurobiological effects of aerobic exercise, with a focus on patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2019 Aug;269(5):499-515. doi: 10.1007/s00406-019-01025-w. Epub 2019 May 21.
- Background: PubMed 38200429Li J, Wang L, Wang Z, Zhao F, Sun Y, Lu Y, Yang L. Association between suicide attempts and anemia in late-life depression inpatients. BMC Geriatr. 2024 Jan 10;24(1):43. doi: 10.1186/s12877-023-04649-9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Erum Tanveer principal investigator
Ziauddin University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aerobic Exercises + Vitamin E, Resistance Exercises + Vitamin E and Aerobic Exercises + Vitamin D in people with Depression Disorders, run by Ziauddin University at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 15 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glutathione Peroxidase and Superoxide Dismutase (time frame: Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06775548, which also lists 31 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2025.