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Chronic PeriodontitisPhase 4NCT04274244

Comparison of Clinical and Radiographic Parameters in the Application of Cross-linked Hyaluronic Acid 1.8% and Enamel Matrix Derivative in Periodontal Regeneration.

A Phase 4 study testing Cross-Linked Hyaluronate Gel Prefilled Syringe 30 MG/3ML and Enamel Matrix Proteins (Active comparator group) in people with Chronic Periodontitis and Periodontal Bone Loss, run by Andres Lopez Roldan at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim of this study is to compare the effectiveness in periodontal regeneration of cross-linked hyaluronic acid at 1.8% (Hyadent BG®) with enamel matrix derivative (Emdogain®) in periodontal bone defects evaluating their clinical and radiographic variables. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Chronic Periodontitis, Periodontal Bone Loss
What is being tested?
Cross-Linked Hyaluronate Gel Prefilled Syringe 30 MG/3ML and Enamel Matrix Proteins (Active comparator group)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteSpain
Study dates
1 Mar 2020to 30 Dec 2024
Phase
Phase 4
Are there results?
None posted in the registry

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 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Periodontitis stage II or III, grade A or B: based on the "Consensus report of workgroup of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions" Tonetti 2017. Clinical attachment loss of 3-5mm, radiographic bone loss to the middle third, loss of teeth ≤4 due to periodontitis, probing depth ≥ 6 mm.
  • At least, 20 teeth in the mouth.
  • Plaque Index (PI) < 1, following initial nonsurgical periodontal therapy and hygiene instructions.
  • At least one interproximal 2, 3-wall bone defect with moderate to deep intrabony defects (≥3mm) on the radiographs, and clinical probing depths (PD) >5mm using William's graduated periodontal probe on premolars or molars following initial nonsurgical periodontal therapy.
  • Absence of caries or overflowing restorations and periapical injuries of the target tooth.
  • Non-smokers.
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  • Absence of systemic disease.
  • Negative history for pregnancy
  • No relevant medical history that contraindicate periodontal surgery.
  • All participants signed an inform consent form.
  • The participant is female or male adult of ≥ 18 years. The sample in sex will be compensated.
  • The participant is willing and able to return to the treatments and evaluations programmed throughout this clinical study.

Who cannot join

  • The participant is pregnant or lactating or plans to become pregnant within the next 6 months.
  • Heavy smoker (>10 cigarettes/day).
  • The participant takes> 4 U of alcohol / day.
  • The participant has a chronic illness or decreased mental capacity which would mitigate the ability to comply with the protocol.
  • Taking drugs that could alter the participant's response in healing or with oral concomitant manifestations that, in the opinion of the investigator, could interfere with the assessment of safety or efficacy.
  • Participants with systemic diseases that interfere with treatment such as, Diabetes mellitus, or rheumatoid arthritis.
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  • Allergies to drug compounds.
  • The participant has been treated with antibiotics within 3 months before starting the study or has any other systemic condition that requires antibiotic coverage for routine periodontal procedures (eg, heart disease, prosthetic joints, etc.).
  • Participants should not have received periodontal tretment within the 6-month period prior to study.

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • University of Valencia

    Valencia, Valencia, 46010

Other trials in Spain

About this study

Official title: Comparison of Clinical and Radiographic Parameters in the Application of Cross-linked Hyaluronic Acid 1.8% (Hyadent BG®) and Enamel Matrix Derivative (Emdogain®) in Periodontal Regeneration: A Randomized Clinical Trial

The aim of this study is to compare the effectiveness in periodontal regeneration of cross-linked hyaluronic acid at 1.8% (Hyadent BG®) with enamel matrix derivative (Emdogain®) in periodontal bone defects evaluating their clinical and radiographic variables.

Read the detailed description

A high molecular weight polysaccharide, hyaluronic acid, also known as hyaluronan or hyaluronate, has recently been studied as a promising mediator for periodontal regeneration. It has a significant role in mineralized and non-mineralized periodontal tissues for the functioning of its extracellular matrices. It has a multifunctional role in periodontics including the stimulation of cell migration, proliferation and differentiation and the acceleration of wound healing by stimulating angiogenesis. It is used in surgical procedures due to its osteoinductive potential. HA is a key element in soft periodontal tissues, the gingiva and periodontal ligament, and in hard tissue, such as alveolar bone and cementum. It has many structural and physiological functions within these tissues.

This research proposes two experimental groups to whom one of them will be applied cross-linked hyaluronic acid at 1.8% and another group with enamel matrix derivative, and a control group.

The investigator's hypothesis is that the hyaluronic acid shows potential for periodontal regeneration when evaluating its clinical and radiographic variables and when compared with the use of Enamel matrix derivative.

Being tested
Cross-Linked Hyaluronate Gel Prefilled Syringe 30 MG/3ML, Enamel Matrix Proteins (Active comparator group)
Keywords
Periodontitis, Hyaluronic acid, Periodontal regeneration
Medical subject headings
Chronic Periodontitis, Alveolar Bone Loss, Periodontitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cross-Linked Hyaluronate Gel Prefilled Syringe 30 MG/3MLDrug

    Also called REGENERATIVE PERIODONTAL SURGERY (Test group)

    Regenerative periodontal therapy + Cross-linked hyaluronic acid 1.8%:

    • The modified minimal invasive surgical technique, described by Cortellini 2011, will be used to raise the interdental papilla over the bone defect.
    • Measurement of bone defect with a 0.5mm periodontal probe (PCP-UNC 15, Hu-Friedy Manufacturing, Illinois, USA) to characterize the defect anatomy.
    • Inflammatory tissue will be debrided and the root carefully planed using Gracey curettes.
    • The site will be washed with physiologic sterile solution, dried and the root wil be conditioned with 24% Ethylenediamine tetraacetic acid (EDTA) for two minutes, then the defect area will be carefully rinsed with sterile saline to remove any residual EDTA.
    • Application of Hyadent BG® 1,8% filling the bone defect from the bottom upwards in the test group.
    • Single internal modified mattress suture (5/0 Vicryl, Ethicon).
    • Sutures will be removed after two weeks.

  • Enamel Matrix Proteins (Active comparator group)Drug

    Also called REGENERATIVE PERIODONTAL SURGERY

    Regenerative periodontal therapy + Enamel matrix proteins:

    • The modified minimal invasive surgical technique, described by Cortellini 2011, will be used to raise the interdental papilla over the bone defect.
    • Measurement of bone defect with a 0.5mm periodontal probe (PCP-UNC 15, Hu-Friedy Manufacturing, Illinois, USA) to characterize the defect anatomy.
    • Inflammatory tissue will be debrided and the root carefully planed using Gracey curettes.
    • The site will be washed with physiologic sterile solution, dried and the root wil be conditioned with 24% Ethylenediamine tetraacetic acid (EDTA) for two minutes, then the defect area will be carefully rinsed with sterile saline to remove any residual EDTA.
    • Application of Emdogain® filling the bone defect from the bottom upwards in the active comparator group.
    • Single internal modified mattress suture (5/0 Vicryl, Ethicon).
    • Sutures will be removed after two weeks.
Study groups in NCT04274244
Study groupRoleWhat they receive
Cross-Linked Hyaluronate Gel Prefilled Syringe 30 MG/3MLExperimental1. The study participants will first undergo SCALE AND ROOT PLANING. This procedure is the same as that used in the active comparator group and the control group. 2. Eight weeks following the initial therapy, reevaluation of the intrabony defects in the interproximal sites with a clinical probing depth >5 mm will be performed by radiographs as well as by using William's graduated periodontal probe to confirm the indication for periodontal surgery. Pairs of premolar and molar teeth in the maxilla or the mandible will be randomized to receive the test treatment (REGENERATIVE PERIODONTAL SURGERY with adjunctive hyaluronic acid gel application) or to serve as active comparators (regenerative periodontal surgery with adjunctive enamel matrix derivative application).
Receives: Drug: Cross-Linked Hyaluronate Gel Prefilled Syringe 30 MG/3ML
Enamel Matrix ProteinsActive comparator1. SCALE AND ROOT PLANING 2. REGENERATIVE PERIODONTAL SURGERY: Application of enamel matrix derivative.
Receives: Drug: Enamel Matrix Proteins (Active comparator group)
Scale and root planningNo interventionControl group: Just SCALE AND ROOT PLANING is performed

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical measure: Clinical attachment loss (CAL). Changes will be assessed at 3 time points.

    It is defined as the distance in millimeters between CEJ and the end of the periodontal pocket. The calculation of the depth of the pocket + gingival recession or pocket depth - gingival hyperplasia will be carried out.

    Measured: 1. Baseline, 2. Reevaluation (60 days after root debridement), 3. Second reevaluation (180 days after Periodontal regenerative surgery).

Secondary outcomes (8)

  1. Radiographic measure: Cemento-enamel junction (A1)

    • The cemento-enamel junction (CEJ)of the tooth involved in the intrabony defect.

    Measured: 1. Baseline, 2. Second reevaluation (180 days after Periodontal regenerative surgery).

  2. Radiographic measure: B1

    The most coronal position of the alveolar bone crest of the intrabony defect when it touches the root surface of the adjacent tooth before treatment (the top of the crest).

    Measured: 1. Baseline, 2. Second reevaluation (180 days after Periodontal regenerative surgery).

  3. Radiographic measure: D1

    The most apical extension of the intrabony destruction where the periodontal ligament space still retained its normal width before treatment (the bottom of the defect).

    Measured: 1. Baseline, 2. Second reevaluation (180 days after Periodontal regenerative surgery).

  4. Clinical measure: Probing pocket depth (PPD). Changes will be assessed at 3 time points.

    The probing depth will be measured in six areas (disto-buccal, mediate-vestibular, mesio-buccal, disto-palatal, mid-palatal, and mesio-palatal) of each tooth with a Williams PQ-OW 208 396 probe. It will be use with a pressure of 20 grams that is equivalent to the pressure of dropping the weight of the probe without exerting additional pressure.

    Measured: 1. Baseline, 2. Reevaluation (60 days after Scale and root planing), 3. Second reevaluation (180 days after Periodontal regenerative surgery).

  5. Clinical measure: Gingival recession (GR). Changes will be assessed at 3 time points.

    The "Full mouth bleeding score" (FMBS) will be calculated based on scores of 0 (no bleeding) or 1 (bleeding) after probing depths are checked. The usual thing is to measure 4 points for each tooth, but we have modified the index and we value 6 points per tooth (disto-buccal, mid-buccal, mesio-buccal, disto-palatal, mid-palatal and mesio-palatal).

    We consider that the score is 1 when we see a red dot in the% bleeding diagram of the periodontogram and 0 when we see the blank box.

    Measured: 1. Baseline, 2. Reevaluation (60 days after Scale and root planing), 3. Second reevaluation (180 days after Periodontal regenerative surgery).

  6. Clinical measure: Tooth mobility (TM) Miller (1950). Changes will be assessed at 3 time points.

    • Class I: Mobility up to 1 mm in the horizontal direction.
    • Class II: Mobility greater than 1 mm in the horizontal direction.
    • Class III: Excessive movement in both horizontal and vertical directions.

    Measured: 1. Baseline, 2. Reevaluation (60 days after Scale and root planing), 3. Second reevaluation (180 days after Periodontal regenerative surgery).

  7. Clinical measure: Furcation involvement: Hamp (1975). Changes will be assessed at 3 time points.

    The plaque will be quantified as follows:

    • Score 0 = no plaque
    • Score 1 = A film of plaque adhered to the free gingival margin and the adjacent area of the tooth. The plaque can be seen in situ only after the application of a plaque revealer or by using the probe on the surface of the tooth.
    • Score 2 = moderate accumulation of soft deposits in the pocket, tooth or gingival margin, which can be seen with our eyes.
    • Puntuación 3 = Abundance of soft material inside the bag and / or on the tooth and the gingival margin.

    The evaluation will be carried out in 4 points per tooth (disto-buccal, mesio-buccal, disto-palatal, mesio-palatal).

    Measured: 1. Baseline, 2. Reevaluation (60 days after Scale and root planing), 3. Second reevaluation (180 days after Periodontal regenerative surgery).

  8. Clinical measure: Plaque Index (Sillness y Löe 1964). Changes will be assessed at 3 time points.

    The plaque will be quantified as follows:

    • Score 0 = no plaque
    • Score 1 = A film of plaque adhered to the free gingival margin and the adjacent area of the tooth. The plaque can be seen in situ only after the application of a plaque revealer or by using the probe on the surface of the tooth.
    • Score 2 = moderate accumulation of soft deposits in the pocket, tooth or gingival margin, which can be seen with our eyes.
    • Puntuación 3 = Abundance of soft material inside the bag and / or on the tooth and the gingival margin.

    The evaluation will be carried out in 4 points per tooth (disto-buccal, mesio-buccal, disto-palatal, mesio-palatal).

    Measured: 1. Baseline, 2. Reevaluation (60 days after Scale and root planing), 3. Second reevaluation (180 days after Periodontal regenerative surgery).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2020
  2. Study start1 Mar 2020
  3. Primary completion30 Sep 2024
  4. Study completion30 Dec 2024

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04274244
Sponsor's protocol ID
UV3
Status last verified
Jul 2026
First submitted
9 Apr 2019
Last updated
3 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Rodriguez-A M, Montiel-Company JM, Alpiste-Illueca F, Rodriguez-A L, Paredes-Gallardo V, Lopez-Roldan A. Comparision of crosslinked hyaluronic acid vs. enamel matrix derivative for periodontal regeneration: an 18-month follow-up randomized clinical trial. Clin Oral Investig. 2025 Mar 19;29(4):197. doi: 10.1007/s00784-025-06278-5.

    PubMed 40106008

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Cross-Linked Hyaluronate Gel Prefilled Syringe 30 MG/3ML and Enamel Matrix Proteins (Active comparator group) in people with Chronic Periodontitis and Periodontal Bone Loss, run by Andres Lopez Roldan at 1 site in Spain.

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 12 inclusion and 9 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: finished, as of the sponsor's last update on 3 Aug 2026. 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 Spain. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Clinical measure: Clinical attachment loss (CAL). Changes will be assessed at 3 time points. (time frame: 1. Baseline, 2. Reevaluation (60 days after root debridement), 3. Second reevaluation (180 days after Periodontal regenerative surgery).). 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 NCT04274244, which also lists 1 linked publication.

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 3 Aug 2026.

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