Clinical research protocol · draft for neurologists and Ayurvedic physicians
PRĀṆA–PD feasibility and validation protocol
1. Aims and design
Primary aim. To determine whether the five-domain PRĀṆA–PD assessment can be delivered reliably in routine PD care, and whether inter-domain relationships and individual profiles can be estimated with usable precision.
Secondary aims. (a) Feasibility, adherence and safety of adding standardised, supervised complementary practices (adapted breathing, meditation, adapted yoga, dietary counselling) to usual care. (b) Whether individualised multidisciplinary rehabilitation improves selected domain outcomes. (c) Whether an Ayurvedic assessment adds predictive information beyond conventional measures.
Not an aim. Demonstrating cure, neuroprotection or disease modification.
| Phase | Months | Design | Key outputs |
|---|---|---|---|
| 0 · Foundations | 1–3 | Textual and literature review; expert panel | Definitions and limits of each mapping; draft instrument |
| 1 · Measurement | 4–6 | Delphi consensus; content validity; cognitive interviews with patients | Five-domain instrument v1; Ayurvedic assessment form with defined items |
| 2 · Observational pilot | 7–9 | Single-centre repeated-measures cohort, same-state assessments | Test–retest reliability; inter-rater reliability; domain correlations |
| 3 · Model validation | 10–12 | Analysis of Phase 2 data; simulation-based calibration | Estimates of \(\rho\), \(\mathbf A_C\), \(\mathbf D\) with uncertainty; predictive test vs baseline |
| 4 · Feasibility | 13–15 | Single-arm or small randomised feasibility study of add-on practices (usual care continues) | Recruitment, adherence, retention, adverse events, signal in domain outcomes |
| 5 · Review | 16–18 | Independent review and trial design | Go/no-go; full RCT protocol if justified |
2. Participants
Inclusion (proposed)
- Clinical diagnosis of idiopathic PD by a neurologist (e.g. MDS clinical diagnostic criteria).
- Age ≥ 40; Hoehn & Yahr stages I–III in ON state.
- Stable PD medication for ≥ 4 weeks.
- Able to give informed consent and attend visits.
Exclusion (proposed)
- Atypical or secondary parkinsonism.
- Unstable cardiopulmonary disease; uncontrolled orthostatic hypotension with syncope.
- Recent aspiration pneumonia or severe dysphagia unmanaged by a swallowing team.
- Dementia that prevents consent or safe participation.
- Use of any L-DOPA-containing supplement (e.g. Mucuna pruriens) or unregulated herbal/mineral preparation.
- Pregnancy is not expected in this population.
3. Schedule of assessments
Standardisation rule. Every visit takes place at a fixed time after the morning dose (ON state), and levodopa-equivalent daily dose (LEDD), last-dose time, meals and sleep are recorded, so that medication fluctuation is not mistaken for improvement or decline.
| Domain / outcome | Instrument | Frequency (proposed) |
|---|---|---|
| Prāṇa | Respiratory pattern; spirometry if indicated; olfaction (screening); sensory items | Baseline, every 3 months in Phase 2; monthly in Phase 4 |
| Apāna | Bristol Stool Form Scale + 7-day bowel diary; SCOPA-AUT (GI/urinary items) | Weekly diary, monthly SCOPA-AUT |
| Samāna | Nutrition screen, weight, appetite/GI symptoms; dose–meal timing log | Monthly |
| Vyāna | MDS-UPDRS III, 10-metre walk, Timed Up and Go, seated/standing BP (orthostatic) | Monthly (UPDRS III every 3 months) |
| Udāna | Speech intelligibility rating, EAT-10, clinical swallow screen; referral for instrumental assessment if indicated | Monthly |
| Global outcomes | MDS-UPDRS I–IV, PDQ-39, ADL, patient-defined goals | Baseline, 3-monthly |
| Paired perception (optional) | Sākṣī check-in: measured vs reported per domain (discordance) | Weekly, home |
| Ayurvedic assessment | Standardised Vata/Pitta/Kapha, Agni, Āma, Dhātu, Ojas items, blinded to domain scores | Baseline and 6 months; two assessors for inter-rater study |
Sample size is to be justified by the statistician. In simulation (see paper), coupling estimates from 60 patients with weekly data had SD about 0.02–0.03 per week, and from 200 patients about 0.01–0.02, with uncorrected bias in some links. Sparser clinic sampling will do worse, so Phase 2/3 conclusions about coupling should be treated as exploratory and descriptive. A typical feasibility phase involves 30–60 participants, but the final number must come from the primary feasibility criteria below.
4. Interventions in Phase 4 (added to usual care)
Usual care, including all PD medication, stays under the treating neurologist. Nothing in this protocol changes, delays or replaces medication.
| Category | Standardised content | Delivered by |
|---|---|---|
| Movement (Vyāna) | Parkinson's-specific physiotherapy: gait, balance, strength, aerobic activity, individualised to fall risk | Physiotherapist |
| Nutrition (Apāna, Samāna) | Dietitian-led plan: fluids, fibre, meal pattern; protein/levodopa timing only if the neurologist and dietitian advise it | Dietitian, with Ayurvedic physician for āhāra counselling |
| Respiratory (Prāṇa) | Gentle, supervised diaphragmatic and paced breathing; no breath retention and no forceful or rapid breathing techniques | Physiotherapist / trained instructor |
| Speech and swallowing (Udāna) | Speech-language therapy per local PD standards (e.g. voice-loudness training), swallowing rehabilitation | Speech-language therapist |
| Mind–body | Standardised meditation and relaxation programme, seated or lying | Trained instructor |
| Ayurvedic adjunct | Phase 4 limited to non-ingestible or dietary-routine elements (e.g. daily routine counselling, adapted yoga). Ingestible herbal or mineral preparations are excluded in feasibility. Any later phase must use batch-tested products with certificates of analysis for heavy metals and a pharmacology review. | Qualified Ayurvedic physician |
5. Safety and stopping rules
- Red flags prompt same-day clinical assessment: new choking or coughing with meals, a wet voice, recurrent chest infections, unexplained weight loss, syncope, new chest pain or breathlessness, falls with injury. Severe choking or breathing difficulty is an emergency.
- Adverse events recorded and graded at each contact; serious events reported to the ethics committee per local rules.
- Participant-level stopping: any serious adverse event plausibly related to a study component; participant request; clinician decision.
- Study-level review: an independent safety monitor (not on the study team) reviews events before each phase transition.
- Exercise intensity and breathing practice are adapted to cardiopulmonary assessment, and the physiotherapist can reduce or stop any activity.
- Constipation that persists is investigated medically, not presumed to be a "Vata" disturbance.
6. Analysis plan (to be finalised and pre-registered)
- Reliability (H1). Intraclass correlation (test–retest, inter-rater), standard error of measurement, minimal detectable change per domain; internal consistency where multi-item.
- Associations (H2). Correlation and multivariable regression of domain scores against symptoms, adjusting for age, disease duration, LEDD and stage.
- Coordination (H3). Test whether inter-domain coordination measures add predictive information beyond single-domain scores (likelihood-ratio/AIC, cross-validated error). Dynamic network and state-space models per the paper's estimator, with simulation-based calibration under the actual sampling design before interpreting any coupling value, because bias of 60–90 % was observed in some simulated links.
- Rehabilitation (H4). Linear mixed-effects models of domain outcomes over time; effect sizes with confidence intervals; no multiplicity-free claims.
- Adjuncts (H5). Descriptive in feasibility; formal comparison only in a later adequately powered randomised trial.
- Prediction (H6). Compare the model with a conventional baseline using temporally held-out data and an external validation cohort; report calibration, not only discrimination.
- Missing data and noise. Multiple imputation sensitivity analyses; measurement-error handling for instrument noise.
Feasibility criteria (proposed; to be set by the team before starting)
- Recruitment rate and consent rate.
- Retention at end of Phase 4.
- Adherence to each practice (attendance, home log).
- Assessment completion rate, time per visit.
- Adverse event incidence by category.
7. Ethics, governance and data
- Conducted under the Declaration of Helsinki and applicable national guidance; institutional ethics committee approval before enrolment; prospective registry entry.
- Written informed consent that states plainly that the study does not test a cure and that medication must not be altered.
- Data minimisation and encryption; the Sākṣī app, if used, stores data locally on the participant's device unless a separate approved data pipeline exists. No audio is stored.
- Patient and carer involvement in outcome selection and in weights for the objective function \(\mathbf Q\), \(\mathbf R\), \(\lambda\).
- Roles: neurologist (eligibility, medical oversight), Ayurvedic physician (assessment and standardised practices), physiotherapist, speech-language therapist, dietitian, statistician, independent safety monitor.
8. Dissemination
Results will be reported regardless of outcome, with the model's limitations. Claims will be confined to what the data support: feasibility, reliability, associations and functional outcomes, and never cure or reversal of disease.