Effect of Vitamin C on Collagen Production in Comparison to Hereditary Gingival Fibromatosis: Histopathological Study

NCT ID: NCT07043985

Last Updated: 2025-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-03
• Study Completion Date: 2025-05-06

Brief Summary

In this preliminary study, we propose that the intraepidermic injection of vit C can induce quantitative and qualitative modification of the gingival biotype. We also propose that such improvement is lacking of any pathologic transformation when will compare to the hereditary gingival fibromatosis with highlighting the mechanism of fibrous tissue formation. The study aims secondly to provide a detailed explanation for the pathogenesis of HGF.

Detailed Description

Oral fibromatosis is a benign non-relevant condition that could be an idiopathic solitary manifestation, part of a syndrome or a manifestation associated with systemic disease as leukemia, epilepsy, etc. (Anegundi et al., 2006 and Hakkinen & Csiszar, 2007). It may be also associated with other minor manifestations as hypertrichosis (Pavone, 2015 and Sabina-Pena-Borges, 2015), anemia, gastro-intestinal disturbance and/ or hormonal disturbance. Up till now, the idiopathic form is a rare condition with no definite hypothesis that could explain its mechanism.

Clinically, the disease usually develop as fibrotic non-painful, pinkish, non-hemorrhagic lesions which can either relate to erupted teeth (deciduous or permanent) or edentulous areas (retromolar region, maxillary tuberosity). The lesions primarily erupt as nodular separate islands related to the interproximal papillae then gradually coalesce (Anegundi et al., 2006; Singhal, 2013 and Gawron et al., 2016).

By the development of such lesions, bad esthetics, speech problems, mastication problems, carious lesions, plaque accumulation are the main complaints of the patients suffer from. Bone loss as well as periodontitis may develop later on as a squeal of plaque accumulation and improper cleaning (Ramer et al., 1996 and Anegundi et al., 2006). The peak of enlargement usually accompanies the beginning of mixed dentition (Anegundi et al., 2006; Singhal, 2013 and Gawron et al., 2016).

According to literature, the genetic susceptibility showed the most reliable explanation to fibromatosis development. It may be transmitted as an autosomal dominant or recessive trait. Local factors also play an important role in disease exacerbation such as plaque, calculus, chemical agents, trauma, restorations, orthodontic appliances, fixed restorations (Anegundi et al., 2006).

Histologically, there is great debate if the enlargement's origin is more relevant to epidermis layer, dermis layer or both. In the epidermal theory, the epithelial layer is the initiating layer due to the epithelial mesenchyme transitions and the presence of keratinocyte growth factor (Boukamp et al., 1990) while in the dermal theory, the overproduction of the dense, fibrous and avascular extracellular matrix with differently oriented collagen bundles, marked reduction in collagenase formation are the initiating factors (Vardar et al., 2005; El-Firt, 2011; Pego et al., 2015). The name fibromatosis is related to the dermal hypothesis due to the over production of fibrous tissues. Finally, the coexistence of epithelial and connective tissue hyperplasia regards to fibroblasts and keratinocytes hyperactivity which supports the third theory (Boukamp et al., 1990).

Away from the pathological conditions, gingival thickness could be intentionally induced to modify the oral tissue biotype using vitamin C (vit C), which has antioxidant and anti-inflammatory properties (Yussif et al., 2016). On microscopic examination, vitamin C tissue modification histologically resembles gingival fibromatosis. Therefore, it is quite important to cautiously examine the biotype modification occurs during vitamin C injection.

Gingival tissue biotype exhibits great clinical significance in preserving the gingival health, determining the treatment outcome and the prognosis of periodontal apparatus (Abraham et al., 2014).

Conditions

Tissue Modification After Vit c Injection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

G1 (positive control): 5 patients suffering from non-syndromic HGF

Gingival bioposy was evaluated

Group Type: EXPERIMENTAL

biopsy

Intervention Type: DIAGNOSTIC_TEST

Diagnosis of the HGF and healthy tissues depends on pre-described criteria; gingival overgrowth covering one third of the crown length as a minimum, systemically free, no history of drug uptake causing gingival overgrowth (nifedipine, phenytoin, cyclosporine, oral contraceptive pills). Before sampling, written consents were obtained from all patients. Using light microscope, haematoxylin and eosin (H\&E) stained sections were precisely examined and histopathological features were reported. All specimens were assessed semi-quantitatively, on a graded scale, under ×100 magnification power and a fixed grid for the following parameters. Three to four fields of each gingival specimen were randomly selected. A blinded evaluation was done by two independent observers. If a debate was reported regarding a specimen, a consensus was reached following re-evaluation. The most representative areas were selected to be morphometrically analyzed using Leica QWin 500 analyzer computer system (Germany).

G2 (negative control): 5 patients of normal healthy gingival tissue (negative control)

normal healthy gingival tissue biopsy

Group Type: EXPERIMENTAL

biopsy

Intervention Type: DIAGNOSTIC_TEST

Diagnosis of the HGF and healthy tissues depends on pre-described criteria; gingival overgrowth covering one third of the crown length as a minimum, systemically free, no history of drug uptake causing gingival overgrowth (nifedipine, phenytoin, cyclosporine, oral contraceptive pills). Before sampling, written consents were obtained from all patients. Using light microscope, haematoxylin and eosin (H\&E) stained sections were precisely examined and histopathological features were reported. All specimens were assessed semi-quantitatively, on a graded scale, under ×100 magnification power and a fixed grid for the following parameters. Three to four fields of each gingival specimen were randomly selected. A blinded evaluation was done by two independent observers. If a debate was reported regarding a specimen, a consensus was reached following re-evaluation. The most representative areas were selected to be morphometrically analyzed using Leica QWin 500 analyzer computer system (Germany).

received intraepidermic vitamin C injection for non-inflammatory purpose

vit C injection for non-inflammatory purpose

Group Type: ACTIVE_COMPARATOR

biopsy

Intervention Type: DIAGNOSTIC_TEST

Diagnosis of the HGF and healthy tissues depends on pre-described criteria; gingival overgrowth covering one third of the crown length as a minimum, systemically free, no history of drug uptake causing gingival overgrowth (nifedipine, phenytoin, cyclosporine, oral contraceptive pills). Before sampling, written consents were obtained from all patients. Using light microscope, haematoxylin and eosin (H\&E) stained sections were precisely examined and histopathological features were reported. All specimens were assessed semi-quantitatively, on a graded scale, under ×100 magnification power and a fixed grid for the following parameters. Three to four fields of each gingival specimen were randomly selected. A blinded evaluation was done by two independent observers. If a debate was reported regarding a specimen, a consensus was reached following re-evaluation. The most representative areas were selected to be morphometrically analyzed using Leica QWin 500 analyzer computer system (Germany).

G4: 5 patients received vitamin C injection for inflammatory purposes

vitamin C injection for inflammatory purposes

Group Type: ACTIVE_COMPARATOR

biopsy

Intervention Type: DIAGNOSTIC_TEST

Diagnosis of the HGF and healthy tissues depends on pre-described criteria; gingival overgrowth covering one third of the crown length as a minimum, systemically free, no history of drug uptake causing gingival overgrowth (nifedipine, phenytoin, cyclosporine, oral contraceptive pills). Before sampling, written consents were obtained from all patients. Using light microscope, haematoxylin and eosin (H\&E) stained sections were precisely examined and histopathological features were reported. All specimens were assessed semi-quantitatively, on a graded scale, under ×100 magnification power and a fixed grid for the following parameters. Three to four fields of each gingival specimen were randomly selected. A blinded evaluation was done by two independent observers. If a debate was reported regarding a specimen, a consensus was reached following re-evaluation. The most representative areas were selected to be morphometrically analyzed using Leica QWin 500 analyzer computer system (Germany).

Interventions

biopsy

Diagnosis of the HGF and healthy tissues depends on pre-described criteria; gingival overgrowth covering one third of the crown length as a minimum, systemically free, no history of drug uptake causing gingival overgrowth (nifedipine, phenytoin, cyclosporine, oral contraceptive pills). Before sampling, written consents were obtained from all patients. Using light microscope, haematoxylin and eosin (H\&E) stained sections were precisely examined and histopathological features were reported. All specimens were assessed semi-quantitatively, on a graded scale, under ×100 magnification power and a fixed grid for the following parameters. Three to four fields of each gingival specimen were randomly selected. A blinded evaluation was done by two independent observers. If a debate was reported regarding a specimen, a consensus was reached following re-evaluation. The most representative areas were selected to be morphometrically analyzed using Leica QWin 500 analyzer computer system (Germany).

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• patients diagnosed as HGF
• patients diagnosed with altered passive eruption who needs excess gingival tissue removal
• no age or gender predilection

Exclusion Criteria

• patienst undertaken drugs cause gingival enlargment
• prednent and lactating mothers

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cairo University

OTHER

Sponsor Role: collaborator

Badr University

OTHER

Sponsor Role: lead

Responsible Party

Rasha Wagih

assistant professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Entertainment Area, Badr City, Cairo, Egypt

Cairo, , Egypt

Countries

Egypt

Other Identifiers

BUC-IACUC-250423-130

Identifier Type: -

Identifier Source: org_study_id